Inflammation-induced Id2 promotes plasticity in regulatory T cells

Sung-Min Hwang, Garima Sharma, Ravi Verma, Seohyun Byun, Dipayan Rudra () and Sin-Hyeog Im ()
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Sung-Min Hwang: Institute for Basic Science (IBS)
Garima Sharma: Institute for Basic Science (IBS)
Ravi Verma: Institute for Basic Science (IBS)
Seohyun Byun: Institute for Basic Science (IBS)
Dipayan Rudra: Institute for Basic Science (IBS)
Sin-Hyeog Im: Institute for Basic Science (IBS)

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-07254-2

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