| First Author | Wang T | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 5 | Pages | 114222 |
| PubMed ID | 38735046 | Mgi Jnum | J:350659 |
| Mgi Id | MGI:7658732 | Doi | 10.1016/j.celrep.2024.114222 |
| Citation | Wang T, et al. (2024) The histone lysine methyltransferase MLL1 regulates the activation and functional specialization of regulatory T cells. Cell Rep 43(5):114222 |
| abstractText | The activation and specialization of regulatory T cells (Tregs) are crucial for maintaining immune self-tolerance; however, the regulation of these processes by histone modifications is not fully understood. Here, we show that T cell-specific deletion of the lysine methyltransferase MLL1 results in a spontaneous lymphocyte proliferation phenotype in aged mice without disturbing the development of conventional T cells and Tregs. Treg-specific MLL1 ablation leads to a systemic autoimmune disease associated with Treg dysfunction. Moreover, RNA sequencing demonstrates that the induction of multiple genes involved in Treg activation, functional specialization, and tissue immigration is defective in MLL1-deficient Tregs. This dysregulation is associated with defects in H3K4 trimethylation at these genes' transcription start sites. Finally, using a T-bet fate-mapping mouse system, we determine that MLL1 is required to establish stable Th1-type Tregs. Thus, MLL1 is essential in optimal Treg function by providing a coordinated chromatin context for activation and specialization. |
