| First Author | Teghanemt A | Year | 2023 |
| Journal | EMBO Rep | Volume | 24 |
| Issue | 5 | Pages | e55543 |
| PubMed ID | 36880575 | Mgi Jnum | J:335733 |
| Mgi Id | MGI:7470657 | Doi | 10.15252/embr.202255543 |
| Citation | Teghanemt A, et al. (2023) DNA demethylation fine-tunes IL-2 production during thymic regulatory T cell differentiation. EMBO Rep 24(5):e55543 |
| abstractText | Regulatory T (T reg) cells developing in the thymus are essential to maintain tolerance and prevent fatal autoimmunity in mice and humans. Expression of the T reg lineage-defining transcription factor FoxP3 is critically dependent upon T cell receptor (TCR) and interleukin-2 (IL-2) signaling. Here, we report that ten-eleven translocation (Tet) enzymes, which are DNA demethylases, are required early during double-positive (DP) thymic T cell differentiation and prior to the upregulation of FoxP3 in CD4 single-positive (SP) thymocytes, to promote Treg differentiation. We show that Tet3 selectively controls the development of CD25(-) FoxP3(lo) CD4SP Treg cell precursors in the thymus and is critical for TCR-dependent IL-2 production, which drive chromatin remodeling at the FoxP3 locus as well as other Treg-effector gene loci in an autocrine/paracrine manner. Together, our results demonstrate a novel role for DNA demethylation in regulating the TCR response and promoting Treg cell differentiation. These findings highlight a novel epigenetic pathway to promote the generation of endogenous Treg cells for mitigation of autoimmune responses. |
