TY - JOUR
T1 - Glucocorticoid receptor signaling in leukocytes after early life adversity
AU - Elwenspoek, Martha M.C.
AU - Hengesch, Xenia
AU - Leenen, Fleur A.D.
AU - Sias, Krystel
AU - Fernandes, Sara Beatriz
AU - Schaan, Violetta K.
AU - Mériaux, Sophie B.
AU - Schmitz, Stephanie
AU - Bonnemberger, Fanny
AU - Schächinger, Hartmut
AU - Vögele, Claus
AU - Muller, Claude P.
AU - Turner, Jonathan D.
N1 - Funding Information:
Financial Support. This study was funded by the Fonds National de Recherche (FNR) Luxembourg (C12/BM/3985792 “EpiPath”; C16/BM/ 11342695 “MetCOEPs”; PRIDE/11012546/NEXTIMMUNE; and an AFR PhD fellowship No 9825384), and the Ministry of Higher Education and Research of Luxembourg, University of Luxembourg, and DFG funding (SCHA1067/3-1) also supported this work. JDT is a management board member of the EU-funded COST actions CM1406, CA16120, and CA18127.
Publisher Copyright:
Copyright © Cambridge University Press 2019.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had 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. Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.
AB - Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had 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. Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.
KW - DNA methylation
KW - FKBP5
KW - GILZ
KW - NR3C1
KW - early life adversity
KW - glucocorticoid receptor
UR - http://www.scopus.com/inward/record.url?scp=85070834856&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/31407649
U2 - 10.1017/S0954579419001147
DO - 10.1017/S0954579419001147
M3 - Article
C2 - 31407649
AN - SCOPUS:85070834856
SN - 0954-5794
VL - 32
SP - 853
EP - 863
JO - Development and Psychopathology
JF - Development and Psychopathology
IS - 3
ER -