DOCK8: regulator of Treg in response to corticotropin-releasing hormone
| Autor: | J. Y. Kim, Jung U Shin, Kwang Hoon Lee, Ji Hye Kim, H.J. Kim, Joong Shik Lee, Shan Jin, Chang Ook Park, Hyunna Lee, Ji Yeon Noh, Noo Ri Lee, Seo Hyeong Kim |
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| Rok vydání: | 2016 |
| Předmět: |
CD4-Positive T-Lymphocytes
Proteomics 0301 basic medicine medicine.medical_specialty Proteome Corticotropin-Releasing Hormone Regulatory T cell Immunology Regulator Gene Expression Inhibitory postsynaptic potential T-Lymphocytes Regulatory Dermatitis Atopic Immunophenotyping Mice 03 medical and health sciences Corticotropin-releasing hormone 0302 clinical medicine Internal medicine Animals Guanine Nucleotide Exchange Factors Humans Immunology and Allergy Medicine Gene knockdown business.industry In vitro Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Case-Control Studies Gene Knockdown Techniques Models Animal Cytokines Female Dock8 business Biomarkers Spleen 030215 immunology Hormone |
| Zdroj: | Allergy. 71:811-819 |
| ISSN: | 0105-4538 |
| DOI: | 10.1111/all.12845 |
| Popis: | 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) by 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. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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