Inflammation-induced Id2 promotes plasticity in regulatory T cells

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....

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Autores principales: Hwang, Sung-Min, Sharma, Garima, Verma, Ravi, Byun, Seohyun, Rudra, Dipayan, Im, Sin-Hyeog
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226514/
https://www.ncbi.nlm.nih.gov/pubmed/30413714
http://dx.doi.org/10.1038/s41467-018-07254-2
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author Hwang, Sung-Min
Sharma, Garima
Verma, Ravi
Byun, Seohyun
Rudra, Dipayan
Im, Sin-Hyeog
author_facet Hwang, Sung-Min
Sharma, Garima
Verma, Ravi
Byun, Seohyun
Rudra, Dipayan
Im, Sin-Hyeog
author_sort Hwang, Sung-Min
collection PubMed
description 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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spelling pubmed-62265142018-11-13 Inflammation-induced Id2 promotes plasticity in regulatory T cells Hwang, Sung-Min Sharma, Garima Verma, Ravi Byun, Seohyun Rudra, Dipayan Im, Sin-Hyeog Nat Commun Article 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. Nature Publishing Group UK 2018-11-09 /pmc/articles/PMC6226514/ /pubmed/30413714 http://dx.doi.org/10.1038/s41467-018-07254-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hwang, Sung-Min
Sharma, Garima
Verma, Ravi
Byun, Seohyun
Rudra, Dipayan
Im, Sin-Hyeog
Inflammation-induced Id2 promotes plasticity in regulatory T cells
title Inflammation-induced Id2 promotes plasticity in regulatory T cells
title_full Inflammation-induced Id2 promotes plasticity in regulatory T cells
title_fullStr Inflammation-induced Id2 promotes plasticity in regulatory T cells
title_full_unstemmed Inflammation-induced Id2 promotes plasticity in regulatory T cells
title_short Inflammation-induced Id2 promotes plasticity in regulatory T cells
title_sort inflammation-induced id2 promotes plasticity in regulatory t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226514/
https://www.ncbi.nlm.nih.gov/pubmed/30413714
http://dx.doi.org/10.1038/s41467-018-07254-2
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