| First Author | Garg G | Year | 2019 |
| Journal | Cell Rep | Volume | 26 |
| Issue | 7 | Pages | 1854-1868.e5 |
| PubMed ID | 30759395 | Mgi Jnum | J:277464 |
| Mgi Id | MGI:6331036 | Doi | 10.1016/j.celrep.2019.01.070 |
| Citation | Garg G, et al. (2019) Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation. Cell Rep 26(7):1854-1868.e5 |
| abstractText | Foxp3(+) regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. Here, we establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway is dependent on the transcriptional regulator Blimp1, which prevents downregulation of Foxp3 expression and "toxic" gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulates IL-6- and STAT3-dependent Dnmt3a expression and function restraining methylation of Treg cell-specific conserved non-coding sequence 2 (CNS2) in the Foxp3 locus. Consequently, CNS2 is heavily methylated when Blimp1 is ablated, leading to a loss of Foxp3 expression and severe disease. These findings identify a Blimp1-dependent pathway that preserves Treg cell stability in inflamed non-lymphoid tissues. |
