Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis
Through their functional diversification, distinct lineages of CD4+ T cells play key roles in either driving or constraining immune-mediated pathology. Transcription factors are critical in the generation of cellular diversity, and negative regulators antagonistic to alternate fates often act in con...
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| Format: | Online |
| Language: | English |
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2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710737/ |
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pubmed-37107372013-12-27 Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis Roychoudhuri, Rahul Hirahara, Kiyoshi Mousavi, Kambiz Clever, David Klebanoff, Christopher A. Bonelli, Michael Sciume, Giuseppe Zare, Hossein Vahedi, Golnaz Dema, Barbara Yu, Zhiya Liu, Hui Takahashi, Hayato Rao, Mahadev Muranski, Pawel Crompton, Joseph G. Punkosdy, George Bedognetti, Davide Wang, Ena Hoffmann, Victoria Rivera, Juan Marincola, Francesco M. Nakamura, Atsushi Sartorelli, Vittorio Kanno, Yuka Gattinoni, Luca Muto, Akihiko Igarashi, Kazuhiko O’Shea, John J. Restifo, Nicholas P. Article Through their functional diversification, distinct lineages of CD4+ T cells play key roles in either driving or constraining immune-mediated pathology. Transcription factors are critical in the generation of cellular diversity, and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage commitment1. Genetic polymorphisms within a single locus encoding the transcription factor BACH2 are associated with numerous autoimmune and allergic diseases including asthma2, Crohn’s disease3–4, coeliac disease5, vitiligo6, multiple sclerosis7 and type 1 diabetes8. While these associations point to a shared mechanism underlying susceptibility to diverse immune-mediated diseases, a function for Bach2 in the maintenance of immune homeostasis has not been established. Here, we define Bach2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programmes of multiple effector lineages in CD4+ T cells. Bach2 was required for efficient formation of regulatory (Treg) cells and consequently for suppression of lethal inflammation in a manner that was Treg cell dependent. Assessment of the genome-wide function of Bach2, however, revealed that it represses genes associated with effector cell differentiation. Consequently, its absence during Treg polarization resulted in inappropriate diversion to effector lineages. In addition, Bach2 constrained full effector differentiation within Th1, Th2 and Th17 cell lineages. These findings identify Bach2 as a key regulator of CD4+ T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity. 2013-06-02 2013-06-27 /pmc/articles/PMC3710737/ /pubmed/23728300 http://dx.doi.org/10.1038/nature12199 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Roychoudhuri, Rahul Hirahara, Kiyoshi Mousavi, Kambiz Clever, David Klebanoff, Christopher A. Bonelli, Michael Sciume, Giuseppe Zare, Hossein Vahedi, Golnaz Dema, Barbara Yu, Zhiya Liu, Hui Takahashi, Hayato Rao, Mahadev Muranski, Pawel Crompton, Joseph G. Punkosdy, George Bedognetti, Davide Wang, Ena Hoffmann, Victoria Rivera, Juan Marincola, Francesco M. Nakamura, Atsushi Sartorelli, Vittorio Kanno, Yuka Gattinoni, Luca Muto, Akihiko Igarashi, Kazuhiko O’Shea, John J. Restifo, Nicholas P. |
| spellingShingle |
Roychoudhuri, Rahul Hirahara, Kiyoshi Mousavi, Kambiz Clever, David Klebanoff, Christopher A. Bonelli, Michael Sciume, Giuseppe Zare, Hossein Vahedi, Golnaz Dema, Barbara Yu, Zhiya Liu, Hui Takahashi, Hayato Rao, Mahadev Muranski, Pawel Crompton, Joseph G. Punkosdy, George Bedognetti, Davide Wang, Ena Hoffmann, Victoria Rivera, Juan Marincola, Francesco M. Nakamura, Atsushi Sartorelli, Vittorio Kanno, Yuka Gattinoni, Luca Muto, Akihiko Igarashi, Kazuhiko O’Shea, John J. Restifo, Nicholas P. Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis |
| author_facet |
Roychoudhuri, Rahul Hirahara, Kiyoshi Mousavi, Kambiz Clever, David Klebanoff, Christopher A. Bonelli, Michael Sciume, Giuseppe Zare, Hossein Vahedi, Golnaz Dema, Barbara Yu, Zhiya Liu, Hui Takahashi, Hayato Rao, Mahadev Muranski, Pawel Crompton, Joseph G. Punkosdy, George Bedognetti, Davide Wang, Ena Hoffmann, Victoria Rivera, Juan Marincola, Francesco M. Nakamura, Atsushi Sartorelli, Vittorio Kanno, Yuka Gattinoni, Luca Muto, Akihiko Igarashi, Kazuhiko O’Shea, John J. Restifo, Nicholas P. |
| author_sort |
Roychoudhuri, Rahul |
| title |
Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis |
| title_short |
Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis |
| title_full |
Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis |
| title_fullStr |
Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis |
| title_full_unstemmed |
Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis |
| title_sort |
bach2 represses effector programmes to stabilize treg-mediated immune homeostasis |
| description |
Through their functional diversification, distinct lineages of CD4+ T cells play key roles in either driving or constraining immune-mediated pathology. Transcription factors are critical in the generation of cellular diversity, and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage commitment1. Genetic polymorphisms within a single locus encoding the transcription factor BACH2 are associated with numerous autoimmune and allergic diseases including asthma2, Crohn’s disease3–4, coeliac disease5, vitiligo6, multiple sclerosis7 and type 1 diabetes8. While these associations point to a shared mechanism underlying susceptibility to diverse immune-mediated diseases, a function for Bach2 in the maintenance of immune homeostasis has not been established. Here, we define Bach2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programmes of multiple effector lineages in CD4+ T cells. Bach2 was required for efficient formation of regulatory (Treg) cells and consequently for suppression of lethal inflammation in a manner that was Treg cell dependent. Assessment of the genome-wide function of Bach2, however, revealed that it represses genes associated with effector cell differentiation. Consequently, its absence during Treg polarization resulted in inappropriate diversion to effector lineages. In addition, Bach2 constrained full effector differentiation within Th1, Th2 and Th17 cell lineages. These findings identify Bach2 as a key regulator of CD4+ T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity. |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710737/ |
| _version_ |
1611994724183310336 |