[en] Multiple sclerosis (MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system (CNS) mediated by autoreactive T cells directed against myelin antigens. Although the crucial role of adaptive immunity is well established in MS, the contribution of innate immunity has only recently been appreciated. Microglia are the main innate immune cells of the CNS. Similar to other myeloid cells, microglia recognize both exogenous and host-derived endogenous danger signals through pattern recognition receptors (PRRs) localized on their cell surface such as Toll Like receptor 4, or in the cytosol such as NLRP3. The second one is the sensor protein of the multi-molecular NLRP3 inflammasome complex in activated microglia that promotes the maturation and secretion of proinflammatory cytokines, interleukin-1β and interleukin-18. Overactivation of microglia and aberrant activation of the NLRP3 inflammasome have been implicated in the pathogenesis of MS. Indeed, experimental data, together with post-mortem and clinical studies have revealed an increased expression of NLRP3 inflammasome complex elements in microglia and other immune cells. In this review, we focus on microglial NLRP3 inflammasome activation in MS. First, we overview the basic knowledge about MS, microglia and the NLRP3 inflammasome. Then, we summarize studies about microglial NLRP3 inflammasome activation in MS and its animal models. We also highlight experimental therapeutic approaches that target different steps of NLRP inflammasome activation. Finally, we discuss future research avenues and new methods in this rapidly evolving area.
Précision sur le type de document :
Compte rendu
Disciplines :
Sciences du vivant: Multidisciplinaire, généralités & autres
Auteur, co-auteur :
Olcum, Melis; Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus Balcova, Izmir, Turkey
TASTAN, Bora ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuroinflammation Group ; Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus Balcova, Izmir, Turkey, Izmir International Biomedicine and Genome Institute (iBG-Izmir), Dokuz Eylul University Health Campus, Balcova, Izmir, Turkey
Kiser, Cagla; Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus Balcova, Izmir, Turkey, Izmir International Biomedicine and Genome Institute (iBG-Izmir), Dokuz Eylul University Health Campus, Balcova, Izmir, Turkey
Genc, Sermin; Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus Balcova, Izmir, Turkey, Izmir International Biomedicine and Genome Institute (iBG-Izmir), Dokuz Eylul University Health Campus, Balcova, Izmir, Turkey, Department of Neuroscience, Institute of Health and Science, Dokuz Eylul University Health Campus, Balcova, Izmir, Turkey
Genc, Kursad; Department of Neuroscience, Institute of Health and Science, Dokuz Eylul University Health Campus, Balcova, Izmir, Turkey
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
Microglial NLRP3 inflammasome activation in multiple sclerosis.
Date de publication/diffusion :
2020
Titre du périodique :
Advances in Protein Chemistry and Structural Biology
Ajami, B., Samusik, N., Wieghofer, P., Ho, P.P., Crotti, A., Bjornson, Z., et al. Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models. Nature Neuroscience 21 (2018), 541–551.
Aksentijevich, I., Nowak, M., Mallah, M., Chae, J.J., Watford, W.T., Hofmann, S.R., et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): A new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis & Rheumatism 46 (2002), 3340–3348.
Allam, R., Lawlor, K.E., Yu, E.C., Mildenhall, A.L., Moujalled, D.M., Lewis, R.S., et al. Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming. EMBO Reports 15 (2014), 982–990.
Areschoug, T., Gordon, S., Pattern recognition receptors and their role in innate immunity: Focus on microbial protein ligands. Contributions to Microbiology 15 (2008), 45–60.
Arneth, B.M., Impact of B cells to the pathophysiology of multiple sclerosis. Journal of Neuroinflammation, 16, 2019, 128.
Aryanpour, R., Pasbakhsh, P., Zibara, K., Namjoo, Z., Beigi Boroujeni, F., Shahbeigi, S., et al. Progesterone therapy induces an M1 to M2 switch in microglia phenotype and suppresses NLRP3 inflammasome in a cuprizone-induced demyelination mouse model. International Immunopharmacology 51 (2017), 131–139.
Astier, A.L., Meiffren, G., Freeman, S., Hafler, D.A., Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. Journal of Clinical Investigation 116 (2006), 3252–3257.
Bai, H., Yang, B., Yu, W., Xiao, Y., Yu, D., Zhang, Q., Cathepsin B links oxidative stress to the activation of NLRP3 inflammasome. Experimental Cell Research 362 (2018), 180–187.
Bai, X.Y., Wang, X.F., Zhang, L.S., Du, P.C., Cao, Z., Hou, Y., Tetramethylpyrazine ameliorates experimental autoimmune encephalomyelitis by modulating the inflammatory response. Biochemical and Biophysical Research Communications 503 (2018), 1968–1972.
Bar, E., Barak, B., Microglia roles in synaptic plasticity and myelination in homeostatic conditions and neurodevelopmental disorders. Glia, 2019, 10.1002/glia.23637 PMID: 31058364. [Epub ahead of print] Review.
Baranzini, S.E., Oksenberg, J.R., The genetics of multiple sclerosis: From 0 to 200 in 50 years. Trends in genetics 33 (2017), 960–970.
Becker, D.E., Basic and clinical pharmacology of glucocorticosteroids. Anesthesia Progress 60 (2013), 25–31 quiz 32.
Bedoui, Y., Neal, J.W., Gasque, P., The neuro-immune-regulators (NIREGs) promote tissue resilience; a vital component of the host's defense strategy against neuroinflammation. Journal of Neuroimmune Pharmacology 13 (2018), 309–329.
Benedek, G., Meza-Romero, R., Jordan, K., Keenlyside, L., Offner, H., Vandenbark, A.A., HLA-DRalpha1-mMOG-35-55 treatment of experimental autoimmune encephalomyelitis reduces CNS inflammation, enhances M2 macrophage frequency, and promotes neuroprotection. Journal of Neuroinflammation, 12, 2015, 123.
Beynon, V., Quintana, F.J., Weiner, H.L., Activated human CD4+CD45RO+ memory T-cells indirectly inhibit NLRP3 inflammasome activation through downregulation of P2X7R signalling. PLoS One, 7, 2012, e39576.
Billiau, A., Matthys, P., Modes of action of Freund's adjuvants in experimental models of autoimmune diseases. Journal of Leukocyte Biology 70 (2001), 849–860.
Bortolotti, P., Faure, E., Kipnis, E., Inflammasomes in tissue damages and immune disorders after trauma. Frontiers in Immunology, 9, 2018, 1900.
Bossu, P., Salani, F., Cacciari, C., Picchetto, L., Cao, M., Bizzoni, F., et al. Disease outcome, alexithymia and depression are differently associated with serum IL-18 levels in acute stroke. Current Neurovascular Research 6 (2009), 163–170.
Braga, T.T., Forni, M.F., Correa-Costa, M., Ramos, R.N., Barbuto, J.A., Branco, P., et al. Soluble uric acid activates the NLRP3 inflammasome. Scientific Reports, 7, 2017, 39884.
Brambilla, R., The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathologica 137 (2019), 757–783.
Brown, M.A., Weinberg, R.B., Mast cells and innate lymphoid cells: Underappreciated players in CNS autoimmune demyelinating disease. Frontiers in Immunology, 9, 2018, 514.
Browne, P., Chandraratna, D., Angood, C., Tremlett, H., Baker, C., Taylor, B.V., et al. Atlas of multiple sclerosis 2013: A growing global problem with widespread inequity. Neurology 83 (2014), 1022–1024.
Broz, P., Dixit, V.M., Inflammasomes: Mechanism of assembly, regulation and signalling. Nature Reviews Immunology 16 (2016), 407–420.
Burm, S.M., Peferoen, L.A., Zuiderwijk-Sick, E.A., Haanstra, K.G., T Hart, B.A., Van Der Valk, P., et al. Expression of IL-1beta in rhesus EAE and MS lesions is mainly induced in the CNS itself. Journal of Neuroinflammation, 13, 2016, 138.
Campbell, G., Mahad, D.J., Mitochondrial dysfunction and axon degeneration in progressive multiple sclerosis. FEBS Letters 592 (2018), 1113–1121.
Cantoni, C., Cignarella, F., Ghezzi, L., Mikesell, B., Bollman, B., Berrien-Elliott, M.M., et al. Mir-223 regulates the number and function of myeloid-derived suppressor cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathologica 133 (2017), 61–77.
Centonze, D., Muzio, L., Rossi, S., Cavasinni, F., De Chiara, V., Bergami, A., et al. Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis. Journal of Neuroscience 29 (2009), 3442–3452.
Centonze, D., Muzio, L., Rossi, S., Furlan, R., Bernardi, G., Martino, G., The link between inflammation, synaptic transmission and neurodegeneration in multiple sclerosis. Cell Death & Differentiation 17 (2010), 1083–1091.
Chaix, J., Tessmer, M.S., Hoebe, K., Fuseri, N., Ryffel, B., Dalod, M., et al. Cutting edge: Priming of NK cells by IL-18. The Journal of Immunology 181 (2008), 1627–1631.
Clark, S.J., Lee, H.J., Smallwood, S.A., Kelsey, G., Reik, W., Single-cell epigenomics: Powerful new methods for understanding gene regulation and cell identity. Genome Biology, 17, 2016, 72.
Coll, R.C., Robertson, A.A., Chae, J.J., Higgins, S.C., Munoz-Planillo, R., Inserra, M.C., et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nature Medicine 21 (2015), 248–255.
Colonna, M., Butovsky, O., Microglia function in the central nervous system during Health and neurodegeneration. Annual Review of Immunology 35 (2017), 441–468.
Compeyrot-Lacassagne, S., Tran, T.A., Guillaume-Czitrom, S., Marie, I., Kone-Paut, I., Brain multiple sclerosis-like lesions in a patient with Muckle-Wells syndrome. Rheumatology 48 (2009), 1618–1619.
Constantinescu, C.S., Farooqi, N., O'brien, K., Gran, B., Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). British Journal of Pharmacology 164 (2011), 1079–1106.
Correale, J., Marrodan, M., Ysrraelit, M.C., Mechanisms of neurodegeneration and axonal dysfunction in progressive multiple sclerosis. Biomedicines, 7, 2019.
Csordas, G., Hajnoczky, G., SR/ER-mitochondrial local communication: Calcium and ROS. Biochimica et Biophysica Acta 1787 (2009), 1352–1362.
Cuascut, F.X., Hutton, G.J., Stem cell-based therapies for multiple sclerosis: Current perspectives. Biomedicines, 7, 2019.
Cuevas-Diaz Duran, R., Wei, H., Wu, J.Q., Single-cell RNA-sequencing of the brain. Clinical and Translational Medicine, 6, 2017, 20.
Cui, Y., Wan, Q., NKT cells in neurological diseases. Frontiers in Cellular Neuroscience, 13, 2019, 245.
Danikowski, K.M., Jayaraman, S., Prabhakar, B.S., Regulatory T cells in multiple sclerosis and myasthenia gravis. Journal of Neuroinflammation, 14, 2017, 117.
Das, T., Chen, Z., Hendriks, R.W., Kool, M., A20/Tumor necrosis factor alpha-induced protein 3 in immune cells controls development of autoinflammation and autoimmunity: Lessons from mouse models. Frontiers in Immunology, 9, 2018, 104.
Delbridge, L.M., O'riordan, M.X., Innate recognition of intracellular bacteria. Current Opinion in Immunology 19 (2007), 10–16.
Di Ruscio, A., Patti, F., Welner, R.S., Tenen, D.G., Amabile, G., Multiple sclerosis: Getting personal with induced pluripotent stem cells. Cell Death & Disease, 6, 2015, e1806.
Dinarello, C.A., Overview of the IL-1 family in innate inflammation and acquired immunity. Immunological Reviews 281 (2018), 8–27.
Dubbelaar, M.L., Kracht, L., Eggen, B.J.L., Boddeke, E., The kaleidoscope of microglial phenotypes. Frontiers in Immunology, 9, 2018, 1753.
Evavold, C.L., Kagan, J.C., How inflammasomes inform adaptive immunity. Journal of Molecular Biology 430 (2018), 217–237.
Eyo, U.B., Wu, L.J., Microglia: Lifelong patrolling immune cells of the brain. Progress in Neurobiology, 179, 2019, 101614.
Fann, D.Y., Lee, S.Y., Manzanero, S., Tang, S.C., Gelderblom, M., Chunduri, P., et al. Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke. Cell Death & Disease, 4, 2013, e790.
Faustin, B., Chen, Y., Zhai, D., Le Negrate, G., Lartigue, L., Satterthwait, A., et al. Mechanism of Bcl-2 and Bcl-X(L) inhibition of NLRP1 inflammasome: Loop domain-dependent suppression of ATP binding and oligomerization. Proceedings of the National Academy of Sciences of the U S A 106 (2009), 3935–3940.
Ferrari, C.C., Depino, A.M., Prada, F., Muraro, N., Campbell, S., Podhajcer, O., et al. Reversible demyelination, blood-brain barrier breakdown, and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain. American Journal Of Pathology 165 (2004), 1827–1837.
Fiebich, B.L., Akter, S., Akundi, R.S., The two-hit hypothesis for neuroinflammation: Role of exogenous ATP in modulating inflammation in the brain. Frontiers in Cellular Neuroscience, 8, 2014, 260.
Filippi, M., Bar-Or, A., Piehl, F., Preziosa, P., Solari, A., Vukusic, S., et al. Multiple sclerosis. Nat Rev Dis Primers, 4, 2018, 43.
Filippi, M., Bruck, W., Chard, D., Fazekas, F., Geurts, J.J.G., Enzinger, C., et al., Attendees of the Correlation Between, P., and Workshop, M.R.I.F.I.M, Association between pathological and MRI findings in multiple sclerosis. The Lancet Neurology 18 (2019), 198–210.
Freeman, L., Guo, H., David, C.N., Brickey, W.J., Jha, S., Ting, J.P., NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes. Journal of Experimental Medicine 214 (2017), 1351–1370.
Fu, Y., Wang, Y., Du, L., Xu, C., Cao, J., Fan, T., et al. Resveratrol inhibits ionising irradiation-induced inflammation in MSCs by activating SIRT1 and limiting NLRP-3 inflammasome activation. International Journal of Molecular Sciences 14 (2013), 14105–14118.
Garlanda, C., Dinarello, C.A., Mantovani, A., The interleukin-1 family: Back to the future. Immunity 39 (2013), 1003–1018.
Genc, B., Bozan, H.R., Genc, S., Genc, K., Stem cell therapy for multiple sclerosis. Advances in Experimental Medicine & Biology 1084 (2019), 145–174, 10.1007/5584_2018_247 PMID: 30039439.
Genc, K., Dona, D.L., Reder, A.T., Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy. Journal of Clinical Investigation 99 (1997), 2664–2671.
Gerhauser, I., Hansmann, F., Ciurkiewicz, M., Loscher, W., Beineke, A., Facets of Theiler's murine encephalomyelitis virus-induced diseases: An update. International Journal of Molecular Sciences, 20, 2019.
Gharagozloo, M., Gris, K.V., Mahvelati, T., Amrani, A., Lukens, J.R., Gris, D., NLR-dependent regulation of inflammation in multiple sclerosis. Frontiers in Immunology, 8, 2017, 2012.
Gong, Z., Pan, J., Shen, Q., Li, M., Peng, Y., Mitochondrial dysfunction induces NLRP3 inflammasome activation during cerebral ischemia/reperfusion injury. Journal of Neuroinflammation, 15, 2018, 242.
Gosselin, D., Rivest, S., Role of IL-1 and TNF in the brain: Twenty years of progress on a Dr. Jekyll/Mr. Hyde duality of the innate immune system. Brain, Behavior, and Immunity 21 (2007), 281–289.
Greaney, A.J., Maier, N.K., Leppla, S.H., Moayeri, M., Sulforaphane inhibits multiple inflammasomes through an Nrf2-independent mechanism. Journal of Leukocyte Biology 99 (2016), 189–199.
Green, J.P., Yu, S., Martin-Sanchez, F., Pelegrin, P., Lopez-Castejon, G., Lawrence, C.B., et al. Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming. Proceedings of the National Academy of Sciences of the U S A 115 (2018), E9371–E9380.
Gris, D., Ye, Z., Iocca, H.A., Wen, H., Craven, R.R., Gris, P., et al. NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. The Journal of Immunology 185 (2010), 974–981.
Groslambert, M., Py, B.F., Spotlight on the NLRP3 inflammasome pathway. Journal of Inflammation Research 11 (2018), 359–374.
Gross, C.C., Schulte-Mecklenbeck, A., Wiendl, H., Marcenaro, E., Kerlero De Rosbo, N., Uccelli, A., et al. Regulatory functions of natural killer cells in multiple sclerosis. Frontiers in Immunology, 7, 2016, 606.
Gross, C.J., Mishra, R., Schneider, K.S., Medard, G., Wettmarshausen, J., Dittlein, D.C., et al. K(+) efflux-independent NLRP3 inflammasome activation by small molecules targeting Mitochondria. Immunity 45 (2016), 761–773.
Guarda, G., Braun, M., Staehli, F., Tardivel, A., Mattmann, C., Forster, I., et al. Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity 34 (2011), 213–223.
Guo, C., Chi, Z., Jiang, D., Xu, T., Yu, W., Wang, Z., et al. Cholesterol homeostatic regulator SCAP-SREBP2 integrates NLRP3 inflammasome activation and cholesterol Biosynthetic signaling in macrophages. Immunity 49 (2018), 842–856 e847.
Guo, C., Fulp, J.W., Jiang, Y., Li, X., Chojnacki, J.E., Wu, J., et al. Development and characterization of a hydroxyl-sulfonamide analogue, 5-chloro-N-[2-(4-hydroxysulfamoyl-phenyl)-ethyl]-2-methoxy-benzamide, as a novel NLRP3 inflammasome inhibitor for potential treatment of multiple sclerosis. ACS Chemical Neuroscience 8 (2017), 2194–2201.
Gurung, P., Anand, P.K., Malireddi, R.K., Vande Walle, L., Van Opdenbosch, N., Dillon, C.P., et al. FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes. The Journal of Immunology 192 (2014), 1835–1846.
Gurung, P., Kanneganti, T.D., Novel roles for caspase-8 in IL-1beta and inflammasome regulation. American Journal Of Pathology 185 (2015), 17–25.
Guttenplan, K.A., Liddelow, S.A., Astrocytes and microglia: Models and tools. Journal of Experimental Medicine 216 (2019), 71–83.
Hanamsagar, R., Torres, V., Kielian, T., Inflammasome activation and IL-1beta/IL-18 processing are influenced by distinct pathways in microglia. Journal of Neurochemistry 119 (2011), 736–748.
Hannocks, M.J., Zhang, X., Gerwien, H., Chashchina, A., Burmeister, M., Korpos, E., et al. The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes. Matrix Biology 75–76 (2019), 102–113.
Harrison, O.J., Srinivasan, N., Pott, J., Schiering, C., Krausgruber, T., Ilott, N.E., et al. Epithelial-derived IL-18 regulates Th17 cell differentiation and Foxp3(+) Treg cell function in the intestine. Mucosal Immunology 8 (2015), 1226–1236.
Hemmer, B., Kerschensteiner, M., Korn, T., Role of the innate and adaptive immune responses in the course of multiple sclerosis. The Lancet Neurology 14 (2015), 406–419.
Heneka, M.T., Kummer, M.P., Latz, E., Innate immune activation in neurodegenerative disease. Nature Reviews Immunology 14 (2014), 463–477.
Hinkle, J.T., Dawson, V.L., Dawson, T.M., The A1 astrocyte paradigm: New avenues for pharmacological intervention in neurodegeneration. Movement Disorders 34 (2019), 959–969.
Hoffman, H.M., Mueller, J.L., Broide, D.H., Wanderer, A.A., Kolodner, R.D., Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nature Genetics 29 (2001), 301–305.
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E.O., Kono, H., Rock, K.L., et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nature Immunology 9 (2008), 847–856.
Huang, W.X., Huang, P., Hillert, J., Increased expression of caspase-1 and interleukin-18 in peripheral blood mononuclear cells in patients with multiple sclerosis. Multiple Sclerosis 10 (2004), 482–487.
Ikegami, A., Haruwaka, K., Wake, H., Microglia: Lifelong modulator of neural circuits. Neuropathology 39 (2019), 173–180.
Imani, D., Azimi, A., Salehi, Z., Rezaei, N., Emamnejad, R., Sadr, M., et al. Association of nod-like receptor protein-3 single nucleotide gene polymorphisms and expression with the susceptibility to relapsing-remitting multiple sclerosis. International Journal of Immunogenetics 45 (2018), 329–336.
Inoue, M., Chen, P.H., Siecinski, S., Li, Q.J., Liu, C., Steinman, L., et al. An interferon-beta-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage. Nature Neuroscience 19 (2016), 1599–1609.
Inoue, M., Shinohara, M.L., NLRP3 inflammasome and MS/EAE. Autoimmune Diseases, 2013, 2013, 859145.
Inoue, M., Williams, K.L., Gunn, M.D., Shinohara, M.L., NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis. Proceedings of the National Academy of Sciences of the U S A 109 (2012), 10480–10485.
Inoue, M., Williams, K.L., Oliver, T., Vandenabeele, P., Rajan, J.V., Miao, E.A., et al. Interferon-beta therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome. Science Signaling, 5, 2012, ra38.
Iyer, S.S., He, Q., Janczy, J.R., Elliott, E.I., Zhong, Z., Olivier, A.K., et al. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity 39 (2013), 311–323.
Jafarzadeh, A., Nemati, M., Therapeutic potentials of ginger for treatment of multiple sclerosis: A review with emphasis on its immunomodulatory, anti-inflammatory and anti-oxidative properties. Journal of Neuroimmunology 324 (2018), 54–75.
Jahanbazi Jahan-Abad, A., Karima, S., Sahab Negah, S., Noorbakhsh, F., Borhani-Haghighi, M., Gorji, A., Therapeutic potential of conditioned medium derived from oligodendrocytes cultured in a self-assembling peptide nanoscaffold in experimental autoimmune encephalomyelitis. Brain Research 1711 (2019), 226–235.
Jha, S., Srivastava, S.Y., Brickey, W.J., Iocca, H., Toews, A., Morrison, J.P., et al. The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. Journal of Neuroscience 30 (2010), 15811–15820.
Johann, S., Heitzer, M., Kanagaratnam, M., Goswami, A., Rizo, T., Weis, J., et al. NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients. Glia 63 (2015), 2260–2273.
Kabba, J.A., Xu, Y., Christian, H., Ruan, W., Chenai, K., Xiang, Y., et al. Microglia: Housekeeper of the central nervous system. Cellular and Molecular Neurobiology 38 (2018), 53–71.
Karni, A., Koldzic, D.N., Bharanidharan, P., Khoury, S.J., Weiner, H.L., IL-18 is linked to raised IFN-gamma in multiple sclerosis and is induced by activated CD4(+) T cells via CD40-CD40 ligand interactions. Journal of Neuroimmunology 125 (2002), 134–140.
Kawana, N., Yamamoto, Y., Ishida, T., Saito, Y., Konno, H., Arima, K., et al. Reactive astrocytes and perivascular macrophages express NLRP3 inflammasome in active demyelinating lesions of multiple sclerosis and necrotic lesions of neuromyelitis optica and cerebral infarction. Clinical and Experimental Neuroimmunology 4 (2013), 296–304.
Ke, P., Shao, B.Z., Xu, Z.Q., Chen, X.W., Wei, W., Liu, C., Activating alpha7 nicotinic acetylcholine receptor inhibits NLRP3 inflammasome through regulation of beta-arrestin-1. CNS Neuroscience and Therapeutics 23 (2017), 875–884.
Keane, R.W., Dietrich, W.D., De Rivero Vaccari, J.P., Inflammasome proteins as biomarkers of multiple sclerosis. Frontiers in Neurology, 9, 2018, 135.
Kettenmann, H., Hanisch, U.K., Noda, M., Verkhratsky, A., Physiology of microglia. Physiological Reviews 91 (2011), 461–553.
Kierdorf, K., Prinz, M., Microglia in steady state. Journal of Clinical Investigation 127 (2017), 3201–3209.
Kipp, M., Nyamoya, S., Hochstrasser, T., Amor, S., Multiple sclerosis animal models: A clinical and histopathological perspective. Brain Pathology 27 (2017), 123–137.
Klaren, R.E., Motl, R.W., Woods, J.A., Miller, S.D., Effects of exercise in experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis). Journal of Neuroimmunology 274 (2014), 14–19.
Klineova, S., Lublin, F.D., Clinical course of multiple sclerosis. Cold Spring Harb Perspect Med, 8, 2018.
Kostic, M., Zivkovic, N., Stojanovic, I., Multiple sclerosis and glutamate excitotoxicity. Reviews in the Neurosciences 24 (2013), 71–88.
Kothur, K., Wienholt, L., Brilot, F., Dale, R.C., CSF cytokines/chemokines as biomarkers in neuroinflammatory CNS disorders: A systematic review. Cytokine 77 (2016), 227–237.
Kumar, H., Kawai, T., Akira, S., Pathogen recognition by the innate immune system. International Reviews of Immunology 30 (2011), 16–34.
Lalor, S.J., Dungan, L.S., Sutton, C.E., Basdeo, S.A., Fletcher, J.M., Mills, K.H., Caspase-1-processed cytokines IL-1beta and IL-18 promote IL-17 production by gammadelta and CD4 T cells that mediate autoimmunity. The Journal of Immunology 186 (2011), 5738–5748.
Lassmann, H., Bradl, M., Multiple sclerosis: Experimental models and reality. Acta Neuropathologica 133 (2017), 223–244.
Laudisi, F., Spreafico, R., Evrard, M., Hughes, T.R., Mandriani, B., Kandasamy, M., et al. Cutting edge: The NLRP3 inflammasome links complement-mediated inflammation and IL-1beta release. The Journal of Immunology 191 (2013), 1006–1010.
Leal-Lasarte, M.M., Franco, J.M., Labrador-Garrido, A., Pozo, D., Roodveldt, C., Extracellular TDP-43 aggregates target MAPK/MAK/MRK overlapping kinase (MOK) and trigger caspase-3/IL-18 signaling in microglia. The FASEB Journal 31 (2017), 2797–2816.
Lee, E., Hwang, I., Park, S., Hong, S., Hwang, B., Cho, Y., et al. MPTP-driven NLRP3 inflammasome activation in microglia plays a central role in dopaminergic neurodegeneration. Cell Death & Differentiation 26 (2019), 213–228.
Leemans, J.C., Cassel, S.L., Sutterwala, F.S., Sensing damage by the NLRP3 inflammasome. Immunological Reviews 243 (2011), 152–162.
Lemasters, J.J., Theruvath, T.P., Zhong, Z., Nieminen, A.L., Mitochondrial calcium and the permeability transition in cell death. Biochimica et Biophysica Acta 1787 (2009), 1395–1401.
Lenz, K.M., Nelson, L.H., Microglia and beyond: Innate immune cells as regulators of brain development and behavioral function. Frontiers in Immunology, 9, 2018, 698.
Li, Q., Barres, B.A., Microglia and macrophages in brain homeostasis and disease. Nature Reviews Immunology 18 (2018), 225–242.
Li, L., Ismael, S., Nasoohi, S., Sakata, K., Liao, F.F., Mcdonald, M.P., et al. Thioredoxin-interacting protein (TXNIP) associated NLRP3 inflammasome activation in human alzheimer's disease brain. Journal of Alzheimer's Disease 68 (2019), 255–265.
Li, Y., Li, J., Li, S., Li, Y., Wang, X., Liu, B., et al. Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK. Toxicology and Applied Pharmacology 286 (2015), 53–63.
Li, K., Li, J., Zheng, J., Qin, S., Reactive astrocytes in neurodegenerative diseases. Aging Dis 10 (2019), 664–675.
Li, R., Patterson, K.R., Bar-Or, A., Reassessing B cell contributions in multiple sclerosis. Nature Immunology 19 (2018), 696–707.
Li, R., Rezk, A., Miyazaki, Y., Hilgenberg, E., Touil, H., Shen, P., et al. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy. Science Translational Medicine, 7, 2015, 310ra166.
Liddelow, S.A., Guttenplan, K.A., Clarke, L.E., Bennett, F.C., Bohlen, C.J., Schirmer, L., et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541 (2017), 481–487.
Lin, C.C., Edelson, B.T., New insights into the role of IL-1beta in experimental autoimmune encephalomyelitis and multiple sclerosis. The Journal of Immunology 198 (2017), 4553–4560.
Lin, Z.H., Wang, S.Y., Chen, L.L., Zhuang, J.Y., Ke, Q.F., Xiao, D.R., et al. Methylene Blue Mitigates acute neuroinflammation after spinal cord injury through inhibiting NLRP3 inflammasome activation in microglia. Frontiers in Cellular Neuroscience, 11, 2017, 391.
Liu, X., Zhang, Z., Ruan, J., Pan, Y., Magupalli, V.G., Wu, H., et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 535 (2016), 153–158.
Liu, X., Zhou, W., Zhang, X., Lu, P., Du, Q., Tao, L., et al. Dimethyl fumarate ameliorates dextran sulfate sodium-induced murine experimental colitis by activating Nrf2 and suppressing NLRP3 inflammasome activation. Biochemical Pharmacology 112 (2016), 37–49.
Liu, Y., Given, K.S., Harlow, D.E., Matschulat, A.M., Macklin, W.B., Bennett, J.L., et al. Myelin-specific multiple sclerosis antibodies cause complement-dependent oligodendrocyte loss and demyelination. Acta Neuropathol Commun, 5, 2017, 25.
Lloyd, A.F., Davies, C.L., Miron, V.E., Microglia: Origins, homeostasis, and roles in myelin repair. Current Opinion in Neurobiology 47 (2017), 113–120.
Lukens, J.R., Barr, M.J., Chaplin, D.D., Chi, H., Kanneganti, T.D., Inflammasome-derived IL-1beta regulates the production of GM-CSF by CD4(+) T cells and gammadelta T cells. The Journal of Immunology 188 (2012), 3107–3115.
Luo, C., Jian, C., Liao, Y., Huang, Q., Wu, Y., Liu, X., et al. The role of microglia in multiple sclerosis. Neuropsychiatric Disease and Treatment 13 (2017), 1661–1667.
Malhotra, S., Rio, J., Urcelay, E., Nurtdinov, R., Bustamante, M.F., Fernandez, O., et al. NLRP3 inflammasome is associated with the response to IFN-beta in patients with multiple sclerosis. Brain 138 (2015), 644–652.
Malhotra, S., Sorosina, M., Rio, J., Peroni, S., Midaglia, L., Villar, L.M., et al. NLRP3 polymorphisms and response to interferon-beta in multiple sclerosis patients. Multiple Sclerosis 24 (2018), 1507–1510.
Malik, A., Kanneganti, T.D., Inflammasome activation and assembly at a glance. Journal of Cell Science 130 (2017), 3955–3963.
Malik, S., Want, M.Y., Awasthi, A., The emerging roles of gamma-delta T cells in tissue inflammation in experimental autoimmune encephalomyelitis. Frontiers in Immunology, 7, 2016, 14.
Mammana, S., Fagone, P., Cavalli, E., Basile, M.S., Petralia, M.C., Nicoletti, F., et al. The role of macrophages in neuroinflammatory and neurodegenerative pathways of alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis: Pathogenetic cellular effectors and potential therapeutic targets. International Journal of Molecular Sciences, 19, 2018.
Mangan, M.S.J., Olhava, E.J., Roush, W.R., Seidel, H.M., Glick, G.D., Latz, E., Targeting the NLRP3 inflammasome in inflammatory diseases. Nature Reviews Drug Discovery 17 (2018), 588–606.
Mao, Z., Liu, C., Ji, S., Yang, Q., Ye, H., Han, H., et al. The NLRP3 inflammasome is involved in the pathogenesis of Parkinson's disease in rats. Neurochemical Research 42 (2017), 1104–1115.
Marinelli, S., Basilico, B., Marrone, M.C., Ragozzino, D., Microglia-neuron crosstalk: Signaling mechanism and control of synaptic transmission. Seminars in Cell & Developmental Biology, 94, 2019 pii: S1084-9521(18)30170-8. https://doi.org/10.1016/j.semcdb.2019.05.017 PMID: 31112798, [Epubahead of print] Review.
Martinon, F., Burns, K., Tschopp, J., The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Molecular Cell 10 (2002), 417–426.
Mccandless, E.E., Budde, M., Lees, J.R., Dorsey, D., Lyng, E., Klein, R.S., IL-1R signaling within the central nervous system regulates CXCL12 expression at the blood-brain barrier and disease severity during experimental autoimmune encephalomyelitis. The Journal of Immunology 183 (2009), 613–620.
Mckenzie, B., Reinke, S., Branton, W., Lu, J.-Q., Power, C., Activation of multiple inflammasomes within the central nervous system during experimental autoimmune encephalomyelitis and multiple sclerosis. Journal of Neuroimmunology, 275, 2014, 163.
Mckenzie, B.A., Mamik, M.K., Saito, L.B., Boghozian, R., Monaco, M.C., Major, E.O., et al. Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis. Proceedings of the National Academy of Sciences of the U S A 115 (2018), E6065–E6074.
Mendiola, A.S., Cardona, A.E., The IL-1beta phenomena in neuroinflammatory diseases. Journal of Neural Transmission 125 (2018), 781–795.
Michailidou, I., Jongejan, A., Vreijling, J.P., Georgakopoulou, T., De Wissel, M.B., Wolterman, R.A., et al. Systemic inhibition of the membrane attack complex impedes neuroinflammation in chronic relapsing experimental autoimmune encephalomyelitis. Acta Neuropathol Commun, 6, 2018, 36.
Michel, L., Touil, H., Pikor, N.B., Gommerman, J.L., Prat, A., Bar-Or, A., B cells in the multiple sclerosis central nervous system: Trafficking and contribution to CNS-compartmentalized inflammation. Frontiers in Immunology, 6, 2015, 636.
Miglio, G., Veglia, E., Fantozzi, R., Fumaric acid esters prevent the NLRP3 inflammasome-mediated and ATP-triggered pyroptosis of differentiated THP-1 cells. International Immunopharmacology 28 (2015), 215–219.
Monteiro, A., Cruto, C., Rosado, P., Martinho, A., Rosado, L., Fonseca, M., et al. Characterization of circulating gamma-delta T cells in relapsing vs remission multiple sclerosis. Journal of Neuroimmunology 318 (2018), 65–71.
Mortezaee, K., Khanlarkhani, N., Beyer, C., Zendedel, A., Inflammasome: Its role in traumatic brain and spinal cord injury. Journal of Cellular Physiology 233 (2018), 5160–5169.
Mortimer, L., Moreau, F., Macdonald, J.A., Chadee, K., NLRP3 inflammasome inhibition is disrupted in a group of auto-inflammatory disease CAPS mutations. Nature Immunology 17 (2016), 1176–1186.
Mouton-Liger, F., Rosazza, T., Sepulveda-Diaz, J., Ieang, A., Hassoun, S.M., Claire, E., et al. Parkin deficiency modulates NLRP3 inflammasome activation by attenuating an A20-dependent negative feedback loop. Glia 66 (2018), 1736–1751.
Mrdjen, D., Pavlovic, A., Hartmann, F.J., Schreiner, B., Utz, S.G., Leung, B.P., et al. High-dimensional single-cell Mapping of central nervous system immune cells reveals distinct myeloid subsets in Health, aging, and disease. Immunity 48 (2018), 380–395 e386.
Mukherjee, S., Chen, L.Y., Papadimos, T.J., Huang, S., Zuraw, B.L., Pan, Z.K., Lipopolysaccharide-driven Th2 cytokine production in macrophages is regulated by both MyD88 and TRAM. Journal of Biological Chemistry 284 (2009), 29391–29398.
Munoz-Planillo, R., Kuffa, P., Martinez-Colon, G., Smith, B.L., Rajendiran, T.M., Nunez, G., K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 38 (2013), 1142–1153.
Nakanishi, K., Unique action of interleukin-18 on T cells and other immune cells. Frontiers in Immunology, 9, 2018, 763.
Noroozi, S., Meimand, H.a.E., Arababadi, M.K., Nakhaee, N., Asadikaram, G., The effects of IFN-beta 1a on the expression of inflammasomes and apoptosis-associated speck-like proteins in multiple sclerosis patients. Molecular Neurobiology 54 (2017), 3031–3037.
Ohl, K., Tenbrock, K., Kipp, M., Oxidative stress in multiple sclerosis: Central and peripheral mode of action. Experimental Neurology 277 (2016), 58–67.
Olsson, T., Barcellos, L.F., Alfredsson, L., Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nature Reviews Neurology 13 (2017), 25–36.
Ormel, P.R., Vieira De Sa, R., Van Bodegraven, E.J., Karst, H., Harschnitz, O., Sneeboer, M.a.M., et al. Microglia innately develop within cerebral organoids. Nature Communications, 9, 2018, 4167.
Panicker, N., Sarkar, S., Harischandra, D.S., Neal, M., Kam, T.I., Jin, H., et al. Fyn kinase regulates misfolded alpha-synuclein uptake and NLRP3 inflammasome activation in microglia. Journal of Experimental Medicine 216 (2019), 1411–1430.
Parkhurst, C.N., Yang, G., Ninan, I., Savas, J.N., Yates, J.R. 3rd, Lafaille, J.J., et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155 (2013), 1596–1609.
Parnell, G.P., Booth, D.R., The multiple sclerosis (MS) genetic risk factors indicate both acquired and innate immune cell subsets contribute to MS pathogenesis and identify novel therapeutic opportunities. Frontiers in Immunology, 8, 2017, 425.
Patel, J., Balabanov, R., Molecular mechanisms of oligodendrocyte injury in multiple sclerosis and experimental autoimmune encephalomyelitis. International Journal of Molecular Sciences 13 (2012), 10647–10659.
Peelen, E., Damoiseaux, J., Muris, A.H., Knippenberg, S., Smolders, J., Hupperts, R., et al. Increased inflammasome related gene expression profile in PBMC may facilitate T helper 17 cell induction in multiple sclerosis. Molecular Immunology 63 (2015), 521–529.
Philips, T., Rothstein, J.D., Oligodendroglia: Metabolic supporters of neurons. Journal of Clinical Investigation 127 (2017), 3271–3280.
Pierson, E.R., Wagner, C.A., Goverman, J.M., The contribution of neutrophils to CNS autoimmunity. Clinical Immunology 189 (2018), 23–28.
Place, D.E., Kanneganti, T.D., Recent advances in inflammasome biology. Current Opinion in Immunology 50 (2017), 32–38.
Plantone, D., Inglese, M., Salvetti, M., Koudriavtseva, T., A perspective of coagulation dysfunction in multiple sclerosis and in experimental allergic encephalomyelitis. Frontiers in Neurology, 9, 2018, 1175.
Pocock, J.M., Piers, T.M., Modelling microglial function with induced pluripotent stem cells: An update. Nature Reviews Neuroscience 19 (2018), 445–452.
Ponath, G., Park, C., Pitt, D., The role of astrocytes in multiple sclerosis. Frontiers in Immunology, 9, 2018, 217.
Praet, J., Guglielmetti, C., Berneman, Z., Van Der Linden, A., Ponsaerts, P., Cellular and molecular neuropathology of the cuprizone mouse model: Clinical relevance for multiple sclerosis. Neuroscience & Biobehavioral Reviews 47 (2014), 485–505.
Py, B.F., Kim, M.S., Vakifahmetoglu-Norberg, H., Yuan, J., Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome activity. Molecular Cell 49 (2013), 331–338.
Rathkey, J.K., Zhao, J., Liu, Z., Chen, Y., Yang, J., Kondolf, H.C., et al. Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis. Sci Immunol, 3, 2018.
Raupach, B., Peuschel, S.K., Monack, D.M., Zychlinsky, A., Caspase-1-mediated activation of interleukin-1beta (IL-1beta) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection. Infection and Immunity 74 (2006), 4922–4926.
Reemst, K., Noctor, S.C., Lucassen, P.J., Hol, E.M., The indispensable roles of microglia and astrocytes during brain development. Frontiers in Human Neuroscience, 10, 2016, 566.
Reu, P., Khosravi, A., Bernard, S., Mold, J.E., Salehpour, M., Alkass, K., et al. The lifespan and turnover of microglia in the human brain. Cell Reports 20 (2017), 779–784.
Rodgers, M.A., Bowman, J.W., Liang, Q., Jung, J.U., Regulation where autophagy intersects the inflammasome. Antioxidants and Redox Signaling 20 (2014), 495–506.
Rossi, S., Furlan, R., De Chiara, V., Motta, C., Studer, V., Mori, F., et al. Interleukin-1beta causes synaptic hyperexcitability in multiple sclerosis. Annals of Neurology 71 (2012), 76–83.
Rothschild, D.E., Mcdaniel, D.K., Ringel-Scaia, V.M., Allen, I.C., Modulating inflammation through the negative regulation of NF-kappaB signaling. Journal of Leukocyte Biology, 2018, 10.1002/JLB.3MIR0817-346RRR PMID:29389019. [Epub ahead of print] Review.
Sarkar, S., Malovic, E., Harishchandra, D.S., Ghaisas, S., Panicker, N., Charli, A., et al. Mitochondrial impairment in microglia amplifies NLRP3 inflammasome proinflammatory signaling in cell culture and animal models of Parkinson's disease. NPJ Parkinsons Dis, 3, 2017, 30.
Schetters, S.T.T., Gomez-Nicola, D., Garcia-Vallejo, J.J., Van Kooyk, Y., Neuroinflammation: Microglia and T Cells get ready to tango. Frontiers in Immunology, 8, 2017, 1905.
Schett, G., Neurath, M.F., Resolution of chronic inflammatory disease: Universal and tissue-specific concepts. Nature Communications, 9, 2018, 3261.
Scheu, S., Ali, S., Mann-Nuttel, R., Richter, L., Arolt, V., Dannlowski, U., et al. Interferon beta-mediated protective functions of microglia in central nervous system Autoimmunity. International Journal of Molecular Sciences, 20, 2019.
Schroder, K., Tschopp, J., The inflammasomes. Cell 140 (2010), 821–832.
Schuh, E., Lohse, P., Ertl-Wagner, B., Witt, M., Krumbholz, M., Frankenberger, M., et al. Expanding spectrum of neurologic manifestations in patients with NLRP3 low-penetrance mutations. Neurol Neuroimmunol Neuroinflamm, 2, 2015, e109.
Sedimbi, S.K., Hagglof, T., Karlsson, M.C., IL-18 in inflammatory and autoimmune disease. Cellular and Molecular Life Sciences 70 (2013), 4795–4808.
Serhan, C.N., Levy, B.D., Resolvins in inflammation: Emergence of the pro-resolving superfamily of mediators. Journal of Clinical Investigation 128 (2018), 2657–2669.
Shao, B.Z., Wei, W., Ke, P., Xu, Z.Q., Zhou, J.X., Liu, C., Activating cannabinoid receptor 2 alleviates pathogenesis of experimental autoimmune encephalomyelitis via activation of autophagy and inhibiting NLRP3 inflammasome. CNS Neuroscience and Therapeutics 20 (2014), 1021–1028.
Shaw, P.J., Lukens, J.R., Burns, S., Chi, H., Mcgargill, M.A., Kanneganti, T.D., Cutting edge: Critical role for PYCARD/ASC in the development of experimental autoimmune encephalomyelitis. The Journal of Immunology 184 (2010), 4610–4614.
Shema, E., Bernstein, B.E., Buenrostro, J.D., Single-cell and single-molecule epigenomics to uncover genome regulation at unprecedented resolution. Nature Genetics 51 (2019), 19–25.
Sie, C., Korn, T., Dendritic cells in central nervous system autoimmunity. Seminars in Immunopathology 39 (2017), 99–111.
Singer, J.W., Fleischman, A., Al-Fayoumi, S., Mascarenhas, J.O., Yu, Q., Agarwal, A., Inhibition of interleukin-1 receptor-associated kinase 1 (IRAK1) as a therapeutic strategy. Oncotarget 9 (2018), 33416–33439.
Soares, J.L., Oliveira, E.M., Pontillo, A., Variants in NLRP3 and NLRC4 inflammasome associate with susceptibility and severity of multiple sclerosis. Mult Scler Relat Disord 29 (2019), 26–34.
Sominsky, L., De Luca, S., Spencer, S.J., Microglia: Key players in neurodevelopment and neuronal plasticity. The International Journal of Biochemistry & Cell Biology 94 (2018), 56–60.
Song, L., Yan, Y., Marzano, M., Li, Y., Studying heterotypic Cell(-)Cell interactions in the human brain using pluripotent stem cell models for neurodegeneration. Cells, 8, 2019.
Song, N., Li, T., Regulation of NLRP3 inflammasome by phosphorylation. Frontiers in Immunology, 9, 2018, 2305.
Song, N., Liu, Z.S., Xue, W., Bai, Z.F., Wang, Q.Y., Dai, J., et al. NLRP3 phosphorylation is an essential priming event for inflammasome activation. Molecular Cell 68 (2017), 185–197 e186.
Spalinger, M.R., Kasper, S., Gottier, C., Lang, S., Atrott, K., Vavricka, S.R., et al. NLRP3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase PTPN22. Journal of Clinical Investigation 126 (2016), 1783–1800.
Stancu, I.C., Cremers, N., Vanrusselt, H., Couturier, J., Vanoosthuyse, A., Kessels, S., et al. Aggregated Tau activates NLRP3-ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded Tau pathology in vivo. Acta Neuropathologica 137 (2019), 599–617.
Surace, M.J., Block, M.L., Targeting microglia-mediated neurotoxicity: The potential of NOX2 inhibitors. Cellular and Molecular Life Sciences 69 (2012), 2409–2427.
Sutterwala, F.S., Haasken, S., Cassel, S.L., Mechanism of NLRP3 inflammasome activation. Annals of the New York Academy of Sciences 1319 (2014), 82–95.
Tai, Y., Wang, Q., Korner, H., Zhang, L., Wei, W., Molecular mechanisms of T cells activation by dendritic cells in autoimmune diseases. Frontiers in Pharmacology, 9, 2018, 642.
Tay, T.L., Savage, J.C., Hui, C.W., Bisht, K., Tremblay, M.-È., Microglia across the lifespan: From origin to function in brain development, plasticity and cognition. The Journal of Physiology 595 (2017), 1929–1945.
Tezcan, G., Martynova, E.V., Gilazieva, Z.E., Mcintyre, A., Rizvanov, A.A., Khaiboullina, S.F., MicroRNA post-transcriptional regulation of the NLRP3 inflammasome in immunopathologies. Frontiers in Pharmacology, 10, 2019, 451.
Thion, M.S., Ginhoux, F., Garel, S., Microglia and early brain development: An intimate journey. Science 362 (2018), 185–189.
Thompson, A.J., Banwell, B.L., Barkhof, F., Carroll, W.M., Coetzee, T., Comi, G., et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. The Lancet Neurology 17 (2018), 162–173.
Tintore, M., Vidal-Jordana, A., Sastre-Garriga, J., Treatment of multiple sclerosis - success from bench to bedside. Nature Reviews Neurology 15 (2019), 53–58.
Tozser, J., Benko, S., Natural compounds as regulators of NLRP3 inflammasome-mediated IL-1beta production. Mediators of Inflammation, 2016, 2016, 5460302.
Triantafilou, K., Hughes, T.R., Triantafilou, M., Morgan, B.P., The complement membrane attack complex triggers intracellular Ca2+ fluxes leading to NLRP3 inflammasome activation. Journal of Cell Science 126 (2013), 2903–2913.
Tschopp, J., Schroder, K., NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production?. Nature Reviews Immunology 10 (2010), 210–215.
Tuusa, J., Raasakka, A., Ruskamo, S., Kursula, P., Myelin-derived and putative molecular mimic peptides share structural properties in aqueous and membrane-like environments. Multiple Sclerosis and Demyelinating Disorders, 2, 2017.
Van Bruggen, D., Agirre, E., Castelo-Branco, G., Single-cell transcriptomic analysis of oligodendrocyte lineage cells. Current Opinion in Neurobiology 47 (2017), 168–175.
Van Kaer, L., Postoak, J.L., Wang, C., Yang, G., Wu, L., Innate, innate-like and adaptive lymphocytes in the pathogenesis of MS and EAE. Cellular and Molecular Immunology 16 (2019), 531–539.
Vidmar, L., Maver, A., Drulovic, J., Sepcic, J., Novakovic, I., Ristic, S., et al. Multiple Sclerosis patients carry an increased burden of exceedingly rare genetic variants in the inflammasome regulatory genes. Scientific Reports, 9, 2019, 9171.
Voet, S., Mc Guire, C., Hagemeyer, N., Martens, A., Schroeder, A., Wieghofer, P., et al. A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation. Nature Communications, 9, 2018, 2036.
Voet, S., Prinz, M., Van Loo, G., Microglia in central nervous system inflammation and multiple sclerosis pathology. Trends in Molecular Medicine 25 (2019), 112–123.
Wallisch, J.S., Simon, D.W., Bayir, H., Bell, M.J., Kochanek, P.M., Clark, R.S.B., Cerebrospinal fluid NLRP3 is increased after severe traumatic brain injury in infants and children. Neurocritical Care 27 (2017), 44–50.
Wang, C., Pan, Y., Zhang, Q.Y., Wang, F.M., Kong, L.D., Quercetin and allopurinol ameliorate kidney injury in STZ-treated rats with regulation of renal NLRP3 inflammasome activation and lipid accumulation. PLoS One, 7, 2012, e38285.
Wang, K., Song, F., Fernandez-Escobar, A., Luo, G., Wang, J.H., Sun, Y., The properties of cytokines in multiple sclerosis: Pros and cons. The American Journal of the Medical Sciences 356 (2018), 552–560.
Wang, J., Wang, J., Wang, J., Yang, B., Weng, Q., He, Q., Targeting microglia and macrophages: A potential treatment strategy for multiple sclerosis. Frontiers in Pharmacology, 10, 2019, 286.
Wang, X., Ma, C., Wu, J., Zhu, J., Roles of T helper 17 cells and interleukin-17 in neuroautoimmune diseases with emphasis on multiple sclerosis and Guillain-Barre syndrome as well as their animal models. Journal of Neuroscience Research 91 (2013), 871–881.
Watson, P.M.D., Kavanagh, E., Allenby, G., Vassey, M., Bioengineered 3D glial cell culture systems and applications for neurodegeneration and neuroinflammation. SLAS Discov 22 (2017), 583–601.
Weber, K., Schilling, J.D., Lysosomes integrate metabolic-inflammatory cross-talk in primary macrophage inflammasome activation. Journal of Biological Chemistry 289 (2014), 9158–9171.
Wolf, S.A., Boddeke, H.W., Kettenmann, H., Microglia in physiology and disease. Annual Review of Physiology 79 (2017), 619–643.
Xu, L., Zhang, C., Jiang, N., He, D., Bai, Y., Xin, Y., Rapamycin combined with MCC950 to treat multiple sclerosis in experimental autoimmune encephalomyelitis. Journal of Cellular Biochemistry 120 (2019), 5160–5168.
Xu, X., Yin, D., Ren, H., Gao, W., Li, F., Sun, D., et al. Selective NLRP3 inflammasome inhibitor reduces neuroinflammation and improves long-term neurological outcomes in a murine model of traumatic brain injury. Neurobiology of Disease 117 (2018), 15–27.
Yadav, S.K., Soin, D., Ito, K., Dhib-Jalbut, S., Insight into the mechanism of action of dimethyl fumarate in multiple sclerosis. Journal of Molecular Medicine (Berlin) 97 (2019), 463–472.
Yamamoto, S., Yamashina, K., Ishikawa, M., Gotoh, M., Yagishita, S., Iwasa, K., et al. Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. Journal of Neuroinflammation, 14, 2017, 142.
Yamasaki, R., Lu, H., Butovsky, O., Ohno, N., Rietsch, A.M., Cialic, R., et al. Differential roles of microglia and monocytes in the inflamed central nervous system. Journal of Experimental Medicine 211 (2014), 1533–1549.
Yang, Y., Wang, H., Kouadir, M., Song, H., Shi, F., Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death & Disease, 10, 2019, 128.
Yeh, H., Ikezu, T., Transcriptional and epigenetic regulation of microglia in Health and disease. Trends in Molecular Medicine 25 (2019), 96–111.
Yeon, S.H., Yang, G., Lee, H.E., Lee, J.Y., Oxidized phosphatidylcholine induces the activation of NLRP3 inflammasome in macrophages. Journal of Leukocyte Biology 101 (2017), 205–215.
Yi, Y.S., Regulatory roles of the caspase-11 non-canonical inflammasome in inflammatory diseases. Immune Netw, 18, 2018, e41.
Yu, H., Wu, M., Lu, G., Cao, T., Chen, N., Zhang, Y., et al. Prednisone alleviates demyelination through regulation of the NLRP3 inflammasome in a C57BL/6 mouse model of cuprizone-induced demyelination. Brain Research 1678 (2018), 75–84.
Yue, Y., Stone, S., Lin, W., Role of nuclear factor kappaB in multiple sclerosis and experimental autoimmune encephalomyelitis. Neural Regen Res 13 (2018), 1507–1515.
Zhang, A.Q., Zeng, L., Gu, W., Zhang, L.Y., Zhou, J., Jiang, D.P., et al. Clinical relevance of single nucleotide polymorphisms within the entire NLRP3 gene in patients with major blunt trauma. Critical Care, 15, 2011, R280.
Zhang, C.J., Jiang, M., Zhou, H., Liu, W., Wang, C., Kang, Z., et al. TLR-stimulated IRAKM activates caspase-8 inflammasome in microglia and promotes neuroinflammation. Journal of Clinical Investigation 128 (2018), 5399–5412.
Zhao, G., Jiang, K., Yang, Y., Zhang, T., Wu, H., Shaukat, A., et al. The potential therapeutic role of mir-223 in Bovine endometritis by targeting the NLRP3 inflammasome. Frontiers in Immunology, 9, 2018, 1916.
Zhou, Y., Lu, M., Du, R.H., Qiao, C., Jiang, C.Y., Zhang, K.Z., et al. MicroRNA-7 targets Nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson's disease. Molecular Neurodegeneration, 11, 2016, 28.
Znalesniak, E.B., Fu, T., Guttek, K., Handel, U., Reinhold, D., Hoffmann, W., Increased cerebral Tff1 expression in two murine models of neuroinflammation. Cellular Physiology and Biochemistry 39 (2016), 2287–2296.
Zrzavy, T., Hametner, S., Wimmer, I., Butovsky, O., Weiner, H.L., Lassmann, H., Loss of 'homeostatic' microglia and patterns of their activation in active multiple sclerosis. Brain 140 (2017), 1900–1913.
