Corticotropin-releasing hormone downregulates IL-10 production by adaptive forkhead box protein 3–negative regulatory T cells in patients with atopic dermatitis - 24/12/11
, Chang Ook Park, MD a, , Wen Hao Wu, PhD a, Ji Young Kim, MS a, Shan Jin, MD a, c, Dashlkhumbe Byamba, MD a, c, Byung Gi Bae, MD a, Seongmin Noh, MD a, Beom Jin Lim, MD, PhD b, c, Ji Yeon Noh, PhD a, c, Kwang Hoon Lee, MD, PhD a, c, ⁎ 
Corresponding author: Kwang Hoon Lee, MD, PhD, Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea.Abstract |
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 TH1, TH2, 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 TH1, TH2, 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 TH2 cells and downregulated IFN-γ production by TH1 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.
Le texte complet de cet article est disponible en PDF.Key words : Corticotropin-releasing hormone, stress, atopic dermatitis, IL-10, forkhead box protein 3, regulatory T cell
Abbreviations used : AD, APC, CFSE, CRH, CRHR, DC, EASI, FITC, FoxP3, GAPDH, HC, HPA, MTT, PE, Treg, TSLP
Plan
| Supported by grants of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A080892 and A101348). |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 1
P. 151 - janvier 2012 Retour au numéro
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