Inflammation-induced Id2 promotes plasticity in regulatory T cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30413714.
- Also identified by DOI 10.1038/s41467-018-07254-2 and PMC identifier 6226514.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
T<sub>H</sub>17 cells originating from regulatory T (T<sub>reg</sub>) cells upon loss of the T<sub>reg-</sub>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 T<sub>H</sub>17' cells, remains unclear. Here we show that pro-inflammatory cytokines enhance the expression of transcription regulator Id2, which mediates cellular plasticity of T<sub>reg</sub> into ex-Foxp3 T<sub>H</sub>17 cells. Expression of Id2 in in vitro differentiated iT<sub>reg</sub> cells reduces the expression of Foxp3 by sequestration of the transcription activator E2A, leading to the induction of T<sub>H</sub>17-related cytokines. T<sub>reg</sub>-specific ectopic expression of Id2 in mice significantly reduces the T<sub>reg</sub> compartment and causes immune dysregulation. Cellular fate-mapping experiments reveal enhanced T<sub>reg</sub> 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 T<sub>reg</sub> cell immunotherapies for both autoimmunity and cancer.
Medical subject headings
- Cell Plasticity
- Inflammation
- Inhibitor of Differentiation Protein 2
- T-Lymphocytes, Regulatory