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Inflammation-induced Id2 promotes plasticity in regulatory T cells

Author

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  • Sung-Min Hwang

    (Institute for Basic Science (IBS)
    Pohang University of Science and Technology (POSTECH))

  • Garima Sharma

    (Institute for Basic Science (IBS)
    Pohang University of Science and Technology (POSTECH))

  • Ravi Verma

    (Institute for Basic Science (IBS))

  • Seohyun Byun

    (Institute for Basic Science (IBS)
    Pohang University of Science and Technology (POSTECH))

  • Dipayan Rudra

    (Institute for Basic Science (IBS)
    Pohang University of Science and Technology (POSTECH))

  • Sin-Hyeog Im

    (Institute for Basic Science (IBS)
    Pohang University of Science and Technology (POSTECH)
    Pohang University of Science and Technology (POSTECH))

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.

Suggested Citation

  • Sung-Min Hwang & Garima Sharma & Ravi Verma & Seohyun Byun & Dipayan Rudra & Sin-Hyeog Im, 2018. "Inflammation-induced Id2 promotes plasticity in regulatory T cells," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07254-2
    DOI: 10.1038/s41467-018-07254-2
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