| First Author | Hwang SM | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 4736 |
| PubMed ID | 30413714 | Mgi Jnum | J:269153 |
| Mgi Id | MGI:6268201 | Doi | 10.1038/s41467-018-07254-2 |
| Citation | Hwang SM, et al. (2018) Inflammation-induced Id2 promotes plasticity in regulatory T cells. Nat Commun 9(1):4736 |
| abstractText | TH17 cells originating from regulatory T (Treg) cells upon loss of the Treg-specific transcription factor Foxp3 accumulate in sites of inflammation and aggravate autoimmune diseases. Whether an active mechanism drives the generation of these pathogenic 'ex-Foxp3 TH17' cells, remains unclear. Here we show that pro-inflammatory cytokines enhance the expression of transcription regulator Id2, which mediates cellular plasticity of Treg into ex-Foxp3 TH17 cells. Expression of Id2 in in vitro differentiated iTreg cells reduces the expression of Foxp3 by sequestration of the transcription activator E2A, leading to the induction of TH17-related cytokines. Treg-specific ectopic expression of Id2 in mice significantly reduces the Treg compartment and causes immune dysregulation. Cellular fate-mapping experiments reveal enhanced Treg plasticity compared to wild-type, resulting in exacerbated experimental autoimmune encephalomyelitis pathogenesis or enhanced anti-tumor immunity. Our findings suggest that controlling Id2 expression may provide a novel approach for effective Treg cell immunotherapies for both autoimmunity and cancer. |
