Article (Scientific journals)
Glucocorticoid receptor signaling in leukocytes after early life adversity.
Elwenspoek, M.; Hengesch, X.; Leenen, F. et al.
2020In Development and Psychopathology, 32 (3), p. 853-863
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Keywords :
Early life adversity; DNA methylation; NR3C1; Glucocorticoid receptor; FKBP5; GILZ
Abstract :
[en] Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA-axis. As the immune system and HPA-axis are tightly intertwined around the glucocorticoid receptor (GR) we examined peripheral GR functionality in the EpiPath cohort, where participants had either been exposed to ELA (separation from parents and/or institutionalization followed by adoption) (n=40) or had been reared by their biological parents (n=72). Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR 1F exon or promoter region, we identified a region of the GR 1H promoter (CpG 1-9) that showed lower methylation levels in ELA. Peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered glucocorticoid receptor response to glucocorticoids. To identify signaling pathways that may underlie the ELA immune phenotype, future research should focus on unbiased approaches, such as investigating whole genome methylation profiles.
Disciplines :
Neurosciences & behavior
Author, co-author :
Elwenspoek, M.
Hengesch, X.
Leenen, F.
Sias, K.
Fernandes, S.
Schaan, Violetta ;  University of Luxembourg > Faculty of Language and Literature, Humanities, Arts and Education (FLSHASE) > Integrative Research Unit: Social and Individual Development (INSIDE)
Mériaux, S.
Schmitz, S.
Bonnemberger, F.
Schächinger, H.
Vögele, Claus ;  University of Luxembourg > Faculty of Language and Literature, Humanities, Arts and Education (FLSHASE) > Integrative Research Unit: Social and Individual Development (INSIDE)
Muller, C.P.
Turner, J.D.
More authors (3 more) Less
External co-authors :
yes
Language :
English
Title :
Glucocorticoid receptor signaling in leukocytes after early life adversity.
Publication date :
2020
Journal title :
Development and Psychopathology
ISSN :
1469-2198
Publisher :
Cambridge University Press, United Kingdom
Volume :
32
Issue :
3
Pages :
853-863
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
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since 27 June 2019

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