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 ADmice model(NC/Nga mice) by using a quantitative proteomicanalysis for the different protein expressions. We found a statistically decreased protein level of DOCK8in CRH treated Tregs from AD mice. In human, DOCK8protein levels were also significantly decreased in CRH treated-Tregs from AD patients. Moreover, the expression of DOCK8in Tregs was inversely correlated with the anxiety levels in the AD patients. In addition to the clinical correlation of DOCK8with the stress level of AD patients, the knockdown of DOCK8in 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 DOCK8expression in Tregs that not only clinically correlates with anxiety levels of AD patients but also regulates suppressive function of Tregs on CD4(+) T cells. This article is protected by copyright. All rights reserved.