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DOCK8: regulator of Treg in response to corticotropin-releasing hormone.

 S. Jin  ;  J. U. Shin  ;  J. Y. Noh  ;  H. Kim  ;  J.Y. Kim  ;  S. H. Kim  ;  J. H. Kim  ;  C. O. Park  ;  N. Lee  ;  H. Lee  ;  J. S. Lee  ;  K. H. Lee 
 ALLERGY, Vol.71(6) : 811-819, 2016 
Journal Title
Issue Date
Animals ; Biomarkers ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Case-Control Studies ; Corticotropin-Releasing Hormone/metabolism* ; Corticotropin-Releasing Hormone/pharmacology ; Cytokines/genetics ; Cytokines/metabolism ; Dermatitis, Atopic/etiology ; Dermatitis, Atopic/immunology ; Dermatitis, Atopic/metabolism ; Disease Models, Animal ; Female ; Gene Expression ; Gene Knockdown Techniques ; Guanine Nucleotide Exchange Factors/genetics ; Guanine Nucleotide Exchange Factors/metabolism* ; Humans ; Immunophenotyping ; Mice ; Models, Animal ; Proteome ; Proteomics ; Spleen/cytology ; Spleen/immunology ; Spleen/metabolism ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism*
atopic dermatitis ; corticotropin-releasing hormone ; dedicator of cytokinesis 8 ; regulatory T cell
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Noh, Ji Yeon(노지연)
Park, Chang Ook(박창욱) ORCID logo https://orcid.org/0000-0003-3856-1201
Shin, Jung U(신정우) ORCID logo https://orcid.org/0000-0001-5259-6879
Lee, Kwang Hoon(이광훈)
Lee, Jungsoo(이정수)
Lee, Hemin(이혜민)
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