Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-07254-2
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Funding
- Institute for Basic Science [IBS-R005-D1]
- Fellowship Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2015H1A2A1030032]
- National Research Foundation of Korea [2015H1A2A1030032] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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T(H)17 cells originating from regulatory T (T-reg) cells upon loss of the T-reg-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(H)17' cells, remains unclear. Here we show that pro-inflammatory cytokines enhance the expression of transcription regulator Id2, which mediates cellular plasticity of T-reg into 'ex-Foxp3' T(H)17 cells. Expression of Id2 in in vitro differentiated iT(reg) cells reduces the expression of Foxp3 by sequestration of the transcription activator E2A, leading to the induction of T(H)17-related cytokines. T-reg-specific ectopic expression of Id2 in mice significantly reduces the T-reg compartment and causes immune dysregulation. Cellular fate-mapping experiments reveal enhanced T-reg 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-reg cell immunotherapies for both autoimmunity and cancer.
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