title: DOCK8: regulator of Treg in response to corticotropin-releasing hormone.
abstract: Atopic dermatitis (AD) is exacerbated by psychological factors, such as stress. We previously reported that corticotrophin-releasing hormone (CRH) treatment in AD patients decreased the proportion of IL-10(+) Tr1 cells, a subset of inducible regulatory T cells (Tregs). However, changes in the function of Tregs in response to CRH have yet to be studied.
  
  
  
  We analyzed the total proteins taken from CRH-treated and untreated Tregs from AD mice model (NC/Nga mice) using a quantitative proteomic analysis for the different protein expressions.
  
  
  
  We found a statistically decreased protein level of DOCK8 in CRH-treated Tregs from AD mice. In human, DOCK8 protein levels were also significantly decreased in CRH-treated Tregs from AD patients. Moreover, the expression of DOCK8 in Tregs was inversely correlated with the anxiety levels in the AD patients. In addition to the clinical correlation of DOCK8 with the stress level of AD patients, the knockdown of DOCK8 in Tregs reduced the inhibitory cytokines, IL-10 and TGF-β, and inhibited the regulatory function of Tregs to suppress the proliferation and TNF-α release of CD4(+) T cells in vitro.
  
  
  
  This study provides new insights on the mechanisms of stress-induced AD aggravation by showing that CRH downregulated DOCK8 expression in Tregs that not only clinically correlates with anxiety levels of AD patients but also regulates suppressive function of Tregs on CD4(+) T cells.
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Department of Dermatology, Yanbian University Hospital, Yanji, Jilin, China.
authors.forename: S
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: J U
authors.initials: JU
authors.lastname: Shin
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Noh
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Mass Spectrometry, Korea Basic Science Institute, Ochang-Myun, Cheongwon-Gun, Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: C O
authors.initials: CO
authors.lastname: Park
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: N
authors.initials: N
authors.lastname: Lee
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D023421:Models, Animal; D020543:Proteome; D040901:Proteomics; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D020543:Proteome; D003346:Corticotropin-Releasing Hormone
keywords: atopic dermatitis; corticotropin-releasing hormone; dedicator of cytokinesis 8; regulatory T cell