Changes in cytokine expression on T cells of patients with atopic dermatitis by corticotropin releasing hormone

Abstract

[한글]

[영문]Corticotropin releasing hormone (CRH) is the central regulating hormone of the hypothalamic-pituitary-adrenal axis, which ultimately synthesizes glucocorticoid as a reaction to stress. CRH is not only released from the central nervous system, but also from various cells making up local tissues. Similarly, CRH receptors are distributed in both neurological and peripheral tissues. Furthermore, CRH is related to the development and aggravation of several cutaneous diseases including urticaria and allergic contact dermatitis. Although atopic dermatitis (AD) is known to be triggered by or exacerbated by stress, the mechanisms by which stress worsens symptoms of AD remain obscure.CRH might directly affect immune cells, such as T cells, which are key effector cells of the immune system. The purpose of this study was to identify the isoforms of CRH receptors (CRH-R) that are located on T cells, to compare the differences in expression of these T cell receptors between AD patients and healthy controls (HCs), and to evaluate the direct effect of CRH on Th1, Th2, and regulatory T cells (Treg). CRH-R1/R2 proteins and mRNAs for CRH-R1α, 1β, and CRH-R2α were found to be expressed on T cells. T cells from patients with AD expressed significantly lower levels of CRH-R1/R2 proteins than did those of HCs. In addition, CRH upregulated IL-4 production by Th2 cells and downregulated IFN-γ production by Th1 cells in HCs. However, the production of IFN-γ and IL-4 in T cells of AD patients did not show any statistical difference between with and without CRH treatment. And there were no significant changes in the polarization of T cells into Th1 and Th2 cells in both HCs and AD patients under 48 h incubation of CRH. CRH also negatively affected Treg cells producing IL-10 (IL-10-secreting Treg type 1 (Tr1) cells) in both HCs and AD patients, and IL-10 production significantly decreased after CRH treatment, especially in patients with AD. These results suggest that the decrease in IL-10 secretion through CRH-mediated Treg cell suppression could partially explain stress-related aggravation of AD.