Social Defeat Modulates T Helper Cell Percentages in Stress Susceptible and Resilient Mice.

Oliver Ambrée,Stefanie Scheu,Volker Arolt,Judith Alferink,Bernhard T Baune,Peter Zwanzger,Luisa Klotz,Christina Ruland

doi:10.3390/ijms20143512

Abstract

Altered adaptive immunity involving T lymphocytes has been found in depressed patients and in stress-induced depression-like behavior in animal models. Peripheral T cells play important roles in homeostasis and function of the central nervous system and thus modulate behavior. However, the T cell phenotype and function associated with susceptibility and resilience to depression remain largely unknown. Here, we characterized splenic T cells in susceptible and resilient mice after 10 days of social defeat stress (SDS). We found equally decreased T cell frequencies and comparably altered expression levels of genes associated with T helper (Th) cell function in resilient and susceptible mice. Interleukin (IL)-17 producing CD4+ and CD8+ T cell numbers in the spleen were significantly increased in susceptible mice. These animals further exhibited significantly reduced numbers of regulatory T cells (Treg) and decreased gene expression levels of TGF-β. Mice with enhanced Th17 differentiation induced by conditional deletion of PPARγ in CD4+ cells (CD4-PPARγKO), an inhibitor of Th17 development, were equally susceptible to SDS when compared to CD4-PPARγWT controls. These data indicate that enhanced Th17 differentiation alone does not alter stress vulnerability. Thus, SDS promotes Th17 cell and suppresses Treg cell differentiation predominantly in susceptible mice with yet unknown effects in immune responses after stress exposure.

Highlights

Stressful life events have been shown to result in long-term alterations of the immune system [1,2,3] and to increase the risk for major depressive disorder (MDD) [4,5]
It is well established that individuals exhibit considerable variability in behavioral responses to stressors, and even genetically identical inbred mouse strains show an individual variability in the sensitivity to social stressors [48]
How specific adaptive immune alterations are correlated with individual stress susceptibility and resilience is poorly characterized

Summary

Introduction

Stressful life events have been shown to result in long-term alterations of the immune system [1,2,3] and to increase the risk for major depressive disorder (MDD) [4,5]. Individuals with MDD have been shown to exhibit altered percentages in circulating Th17 and Treg cells. With regard to Th17 cells, different studies reported increased as well as decreased percentages of circulating Th17 cells in patients with MDD [25,26], while Treg cells were mainly found to be decreased in the peripheral blood [26,27,28]. These findings point towards an imbalance of Th17 and Treg cell populations in MDD

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Results

Conclusion