Inflammation-induced Id2 promotes plasticity in regulatory T cells
SCIE
SCOPUS
- Title
- Inflammation-induced Id2 promotes plasticity in regulatory T cells
- Authors
- Hwang, Sungmin; GARIMA, SHARMA; Verma, Ravi; Byun, Seohyun; Rudra, Dipayan; IM, SIN HYEOG
- Date Issued
- 2018-11
- Publisher
- NATURE PUBLISHING GROUP
- Abstract
- 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.
- Keywords
- doxycycline; inhibitor of differentiation 2; interferon regulatory factor 4; interleukin 1beta; interleukin 6; STAT3 protein; transcription factor E2A; transcription factor FOXP3; cancer; cell component; disease; gene; gene expression; immune response; immune system; immunity; induced response; protein; animal experiment; animal model; Article; autoimmunity; cancer immunotherapy; cell fate; cell plasticity; controlled study; disease exacerbation; ectopic expression; experimental autoimmune encephalomyelitis; female; gene overexpression; immune dysregulation; in vitro study; inflammation; lymphocyte differentiation; melanoma; mouse; neuropathology; nonhuman; nucleotide sequence; regulatory T lymphocyte; Th17 cell; tumor growth; tumor immunity; Mus
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/94265
- DOI
- 10.1038/s41467-018-07254-2
- ISSN
- 2041-1723
- Article Type
- Article
- Citation
- NATURE COMMUNICATIONS, vol. 9, no. 1, 2018-11
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