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

• Published in: Journal of allergy and clinical immunology Vol. 129; no. 1; pp. 151 - 159.e6
• Main Authors: Oh, Sang Ho, Park, Chang Ook, Wu, Wen Hao, Kim, Ji Young, Jin, Shan, Byamba, Dashlkhumbe, Bae, Byung Gi, Noh, Seongmin, Lim, Beom Jin, Noh, Ji Yeon, Lee, Kwang Hoon
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.01.2012; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Allergic diseases; Allergy and Immunology; atopic dermatitis; Biological and medical sciences; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - pharmacology; Cytokines - biosynthesis; Dermatitis, Atopic - genetics; Dermatitis, Atopic - immunology; Dermatitis, Atopic - metabolism; Down-Regulation - drug effects; enzyme-linked immunosorbent assay; Female; Flow cytometry; fluorescent antibody technique; forkhead box protein 3; Forkhead Transcription Factors - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation - drug effects; Humans; IL-10; immunohistochemistry; Immunopathology; interferon-gamma; interleukin-10; Interleukin-10 - biosynthesis; interleukin-4; Lymphocytes; Magnetic fields; Male; Medical sciences; messenger RNA; Neuropeptides; patients; Receptors, Corticotropin-Releasing Hormone - genetics; Receptors, Corticotropin-Releasing Hormone - metabolism; regulatory T cell; reverse transcriptase polymerase chain reaction; RNA, Messenger; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; secretion; Skin allergic diseases. Stinging insect allergies; stress; Stress response; T-lymphocytes; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Th1 Cells - drug effects; Th1 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - immunology; Western blotting; Young Adult; stress; AD; TSLP; CRHR; Treg; atopic dermatitis; CFSE; regulatory T cell; MTT; Corticotropin-releasing hormone; IL-10; forkhead box protein 3; EASI; FITC; APC; PE; CRH; HPA; HC; FoxP3; GAPDH; DC; Fluorescein isothiocyanate; Eczema Area and Severity Index; 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Allophycocyanin; Regulatory T; Healthy control subject; Dendritic cell; Corticotropin-releasing hormone receptor; Hypothalamic-pituitary-adrenal; Thymic stromal lymphopoietin; Carboxyfluorescein succinimidyl ester; Phycoerythrin; Glyceraldehyde-3-phosphate dehydrogenase; Human; Allergy; Immunopathology; Skin disease; Cytokine; Corticotropin releasing factor; Biosynthesis; Protein; Stress; Atopy; Hypothalamic hormone; Immunology; Atopic dermatitis; Interleukin 10; T-Lymphocyte; Hormone releasing factor; Regulatory cell
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2011.09.008

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. We investigated whether CRH directly affects peripheral T H1, T H2, and regulatory T (Treg) cells in patients with AD. 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. 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. CRH-mediated suppression of IL-10 secretion from Treg cells might explain stress-related exacerbations in patients with AD.