Theranostics 2017; 7(4):1002-1009. doi:10.7150/thno.17615

Research Paper

HDAC6 regulates IL-17 expression in T lymphocytes: implications for HDAC6-targeted therapies

Bing Yan1,2*, Yang Liu2*, Hong Bai3, Miao Chen1, Songbo Xie1, Dengwen Li2, Min Liu1, Jun Zhou1,2✉

1. Key Laboratory of Animal Resistance Biology of Shandong Province, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.
2. State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
3. Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
*These authors contributed equally to this work.

Abstract

The pro-inflammatory cytokine interleukin 17 (IL-17) is critically involved in immunity and inflammation. T-helper 17 and γδ T cells are the predominant sources of IL-17 in the immune system. However, the mechanisms by which the expression of IL-17 is regulated in T cells remain elusive. Here, we demonstrate that loss of histone deacetylase 6 (HDAC6) in mice does not affect the generation of CD4+ or CD8+ T cells, but stimulates the development of IL-17-producing γδ T cells. Our data further show that HDAC6 deficiency increases the production of IL-17 by Vγ4+ γδ T cells in the spleen and lymph nodes. Consistent with these observations, small-molecule inhibition of HDAC6 activity in γδ T cells promotes the expression of IL-17 in vitro. These data thus reveal that HDAC6 represses IL-17 production in T cells, providing novel insights into the role of HDAC6 in the immune system. These findings also have important implications for the clinical investigation of HDAC6-targeted therapies.

Keywords: histone deacetylase 6, interleukin 17, T cell, development, knockout mouse.

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How to cite this article:
Yan B, Liu Y, Bai H, Chen M, Xie S, Li D, Liu M, Zhou J. HDAC6 regulates IL-17 expression in T lymphocytes: implications for HDAC6-targeted therapies. Theranostics 2017; 7(4):1002-1009. doi:10.7150/thno.17615. Available from http://www.thno.org/v07p1002.htm