title: Corticotropin-releasing hormone downregulates IL-10 production by adaptive forkhead box protein 3-negative regulatory T cells in patients with atopic dermatitis.
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 T(H)1, T(H)2, 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(H)1, T(H)2, 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(H)2 cells and downregulated IFN-γ production by T(H)1 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.
authors: Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors: Sang Ho
authors: SH
authors: Oh
authors: Chang Ook
authors: CO
authors: Park
authors: Wen Hao
authors: WH
authors: Wu
authors: Ji Young
authors: JY
authors: Kim
authors: Shan
authors: S
authors: Jin
authors: Dashlkhumbe
authors: D
authors: Byamba
authors: Byung Gi
authors: BG
authors: Bae
authors: Seongmin
authors: S
authors: Noh
authors: Beom Jin
authors: BJ
authors: Lim
authors: Ji Yeon
authors: JY
authors: Noh
authors: Kwang Hoon
authors: KH
authors: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D008297:Male; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D055815:Young Adult; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D016753:Interleukin-10; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone