| First Author | Gao B | Year | 2017 |
| Journal | J Immunol | Volume | 198 |
| Issue | 10 | Pages | 3927-3938 |
| PubMed ID | 28424240 | Mgi Jnum | J:247860 |
| Mgi Id | MGI:5926326 | Doi | 10.4049/jimmunol.1600312 |
| Citation | Gao B, et al. (2017) The Histone Acetyltransferase Gcn5 Positively Regulates T Cell Activation. J Immunol 198(10):3927-3938 |
| abstractText | Histone acetyltransferases (HATs) regulate inducible transcription in multiple cellular processes and during inflammatory and immune response. However, the functions of general control nonrepressed-protein 5 (Gcn5), an evolutionarily conserved HAT from yeast to human, in immune regulation remain unappreciated. In this study, we conditionally deleted Gcn5 (encoded by the Kat2a gene) specifically in T lymphocytes by crossing floxed Gcn5 and Lck-Cre mice, and demonstrated that Gcn5 plays important roles in multiple stages of T cell functions including development, clonal expansion, and differentiation. Loss of Gcn5 functions impaired T cell proliferation, IL-2 production, and Th1/Th17, but not Th2 and regulatory T cell differentiation. Gcn5 is recruited onto the il-2 promoter by interacting with the NFAT in T cells upon TCR stimulation. Interestingly, instead of directly acetylating NFAT, Gcn5 catalyzes histone H3 lysine H9 acetylation to promote IL-2 production. T cell-specific suppression of Gcn5 partially protected mice from myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, an experimental model for human multiple sclerosis. Our study reveals previously unknown physiological functions for Gcn5 and a molecular mechanism underlying these functions in regulating T cell immunity. Hence Gcn5 may be an important new target for autoimmune disease therapy. |
