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Glucocorticoid receptor signaling in leukocytes after early life adversity

Published online by Cambridge University Press:  13 August 2019

Martha M. C. Elwenspoek ,
Xenia Hengesch ,
Fleur A. D. Leenen ,
Krystel Sias ,
Sara Beatriz Fernandes ,
Violetta K. Schaan ,
Sophie B. Mériaux ,
Stephanie Schmitz ,
Fanny Bonnemberger  and
Hartmut Schächinger
...Show all authors
Martha M. C. Elwenspoek
Affiliation:
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, L-4354, Grand-Duchy of Luxembourg Department of Immunology, Research Institute of Psychobiology, University of Trier, D-54290Trier, Germany
Xenia Hengesch
Affiliation:
Department of Clinical Psychophysiology, Institute of Psychobiology, University of Trier, Germany
Fleur A. D. Leenen
Affiliation:
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, L-4354, Grand-Duchy of Luxembourg Department of Immunology, Research Institute of Psychobiology, University of Trier, D-54290Trier, Germany
Krystel Sias
Affiliation:
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, L-4354, Grand-Duchy of Luxembourg
Sara Beatriz Fernandes
Affiliation:
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, L-4354, Grand-Duchy of Luxembourg
Violetta K. Schaan
Affiliation:
Institute for Health and Behaviour, Research Unit INSIDE, University of Luxembourg, Grand-Duchy of Luxembourg
Sophie B. Mériaux
Affiliation:
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, L-4354, Grand-Duchy of Luxembourg
Stephanie Schmitz
Affiliation:
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, L-4354, Grand-Duchy of Luxembourg
Fanny Bonnemberger
Affiliation:
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, L-4354, Grand-Duchy of Luxembourg
Hartmut Schächinger
Affiliation:
Department of Clinical Psychophysiology, Institute of Psychobiology, University of Trier, Germany
Claus Vögele
Affiliation:
Institute for Health and Behaviour, Research Unit INSIDE, University of Luxembourg, Grand-Duchy of Luxembourg
Claude P. Muller
Affiliation:
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, L-4354, Grand-Duchy of Luxembourg Department of Immunology, Research Institute of Psychobiology, University of Trier, D-54290Trier, Germany
Jonathan D. Turner*
Affiliation:
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, L-4354, Grand-Duchy of Luxembourg
*
Author for Correspondence: Jonathan D. Turner, Department of Infection and Immunity, Luxembourg Institute of Health, 29 rue Henri Koch, L-4354Esch-sur-Alzette, Grand-Duchy of Luxembourg. E-mail: jonathan.turner@lih.lu
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Abstract

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.

Keywords

DNA methylationearly life adversityFKBP5GILZglucocorticoid receptorNR3C1
Type
Regular Articles
Information
Development and Psychopathology , Volume 32 , Issue 3 , August 2020 , pp. 853 - 863
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Copyright
Copyright © Cambridge University Press 2019

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Footnotes

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Both authors contributed equally as senior authors.

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