S Jin1,2,3, J U Shin1, J Y Noh1, H Kim1, J Y Kim4, S H Kim1,2, J H Kim1, C O Park1, N Lee1,2, H Lee1, J S Lee1, K H Lee1,2. 1. Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea. 2. Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. 3. Department of Dermatology, Yanbian University Hospital, Yanji, Jilin, China. 4. Division of Mass Spectrometry, Korea Basic Science Institute, Ochang-Myun, Cheongwon-Gun, Korea.
Abstract
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.
BACKGROUND:Atopic dermatitis (AD) is exacerbated by psychological factors, such as stress. We previously reported that corticotrophin-releasing hormone (CRH) treatment in ADpatients 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 ADmice 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 ADmice. In human, DOCK8 protein levels were also significantly decreased in CRH-treated Tregs from ADpatients. Moreover, the expression of DOCK8 in Tregs was inversely correlated with the anxiety levels in the ADpatients. In addition to the clinical correlation of DOCK8 with the stress level of ADpatients, 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 ADpatients but also regulates suppressive function of Tregs on CD4(+) T cells.
Authors: Jihee Kim; Tae-Gyun Kim; Si Hyung Lee; Min Kyung Lee; Jong Hoon Kim; Sang Eun Lee; Do Young Kim; Mi Ryung Roh; Chang Ook Park; Ju Hee Lee; Min-Geol Lee; Dongsik Bang; Sang Ho Oh; Kee Yang Chung Journal: Ann Dermatol Date: 2018-08-28 Impact factor: 1.444