HDAC10 deletion promotes Foxp3+ T-regulatory cell function

• Published in: Scientific reports 2020-01, Vol.10 (1), p.424, Article 424
• Main Authors: Dahiya, Satinder, Beier, Ulf H., Wang, Liqing, Han, Rongxiang, Jiao, Jing, Akimova, Tatiana, Angelin, Alessia, Wallace, Douglas C., Hancock, Wayne W.
• Format: Article
• Language: English
• Subjects: 631/250/2520; 631/80/304; 64/60; 692/420/2780/2152; 96; Acetylation; Animals; CD4 antigen; CD8 antigen; Clonal deletion; Colitis; Colitis - genetics; Colitis - immunology; Forkhead Transcription Factors - metabolism; Foxp3 protein; Gene Deletion; Heart transplantation; Heart Transplantation - adverse effects; HEK293 Cells; Histone deacetylase; Humanities and Social Sciences; Humans; Immunotherapy; Inflammatory bowel disease; Inflammatory diseases; Lymphocytes T; Lysine; Major histocompatibility complex; Mice; multidisciplinary; Post-translation; RAG1 protein; Science; Science (multidisciplinary); T-Lymphocytes, Regulatory - cytology; Transcription factors; Transplantation Tolerance - genetics; Transplants & implants
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-57294-x

Foxp3 + T-regulatory (Treg) cells are capable of suppressing immune responses. Lysine acetylation is a key mechanism of post-translational control of various transcription factors, and when acetylated, Foxp3 is stabilized and transcriptionally active. Therefore, understanding the roles of various histone/protein deacetylases (HDAC) are key to promoting Treg-based immunotherapy. Several of the 11 classical HDAC enzymes are necessary for optimal Treg function while others are dispensable. We investigated the effect of HDAC10 in murine Tregs. HDAC10 deletion had no adverse effect on the health of mice, which retained normal CD4 + and CD8 + T cell function. However, HDAC10 −/− Treg exhibited increased suppressive function in vitro and in vivo . C57BL/6 Rag1 −/− mice adoptively transferred with HDAC10 −/− but not wild Treg, were protected from developing colitis. HDAC10 −/− but not wild-type mice receiving fully MHC-mismatched cardiac transplants became tolerant and showed long-term allograft survival (>100 d). We conclude that targeting of HDAC10 may be of therapeutic value for inflammatory disorders including colitis and also for transplantation.