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

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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.

Original languageEnglish
Pages (from-to)811-819
Number of pages9
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume71
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Jin, S., Shin, J. U., Noh, J. Y., Kim, H., Kim, J. Y., Kim, S. H., Kim, J. H., Park, C. O., Lee, N., Lee, H., Lee, J. S., & Lee, K. H. (2016). DOCK8: Regulator of Treg in response to corticotropin-releasing hormone. Allergy: European Journal of Allergy and Clinical Immunology, 71(6), 811-819. https://doi.org/10.1111/all.12845