Corticotropin-releasing hormone downregulates IL-10 production by adaptive forkhead box protein 3-negative regulatory T cells in patients with atopic dermatitis

Background: Corticotropin-releasing hormone (CRH) is the central regulating hormone of the hypothalamic-pituitary-adrenal axis. CRH also has diverse functional effects in the periphery and is related to the aggravation of several cutaneous diseases; however, the effect of CRH on T cells in patients with atopic dermatitis (AD) has not been well evaluated. Objective: We investigated whether CRH directly affects peripheral T_H1, T_H2, and regulatory T (Treg) cells in patients with AD. Methods: We assessed whether T cells express the CRH receptor protein and mRNA by using flow cytometry, Western blotting, immunofluorescence, immunohistochemistry, and RT-PCR. We evaluated cytokine expression using ELISA after treating the T cells extracted from patients with AD and healthy control subjects (HCs) with CRH. Flow cytometry was then used to evaluate any direct effects of CRH on T_H1, T _H2, and Treg cells from patients with AD and HCs. Results: T cells from patients with AD expressed significantly lower CRH receptor 1/2 mRNA levels than T cells from HCs. T cells from HCs reacted with different IL-4 and IFN-γ secretions to CRH treatment, whereas T cells from patients with AD did not. IL-10 production was significantly decreased in the supernatants from both the HCs and patients with AD after CRH treatment. CRH upregulated IL-4 production by T_H2 cells and downregulated IFN-γ production by T_H1 cells in HCs. CRH also suppressed the production of IL-10 by forkhead box protein 3-negative Treg cells in both groups, but the difference was only significant in patients with AD. Conclusions: CRH-mediated suppression of IL-10 secretion from Treg cells might explain stress-related exacerbations in patients with AD.