Inflammation-induced Id2 promotes plasticity in regulatory T cells. Academic Article uri icon

Overview

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.

publication date

  • November 9, 2018

Research

keywords

  • Cell Plasticity
  • Inflammation
  • Inhibitor of Differentiation Protein 2
  • T-Lymphocytes, Regulatory

Identity

PubMed Central ID

  • PMC6226514

Scopus Document Identifier

  • 85056278995

Digital Object Identifier (DOI)

  • 10.1038/nature05543

PubMed ID

  • 30413714

Additional Document Info

volume

  • 9

issue

  • 1