Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation

Katarzyna Karwacz; Emily R. Miraldi; Maria Pokrovskii; Asaf Madi; Nir Yosef; Ivo Wortman; Xi Chen; Aaron Watters; Nicholas Carriero; Amit Awasthi; Aviv Regev; Richard Bonneau; Dan Littman; Vijay K. Kuchroo

doi:10.1038/ni.3683

Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation

Katarzyna Karwacz, Emily R. Miraldi, Maria Pokrovskii, Asaf Madi, Nir Yosef, Ivo Wortman, Xi Chen, Aaron Watters, Nicholas Carriero, Amit Awasthi, Aviv Regev, Richard Bonneau, Dan Littman, Vijay K. Kuchroo

Research output: Contribution to journal › Article › peer-review

Abstract

Type 1 regulatory T cells (Tr1 cells) are induced by interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. We found that the transcription factors IRF1 and BATF were induced early on after treatment with IL-27 and were required for the differentiation and function of Tr1 cells in vitro and in vivo. Epigenetic and transcriptional analyses revealed that both transcription factors influenced chromatin accessibility and expression of the genes required for Tr1 cell function. IRF1 and BATF deficiencies uniquely altered the chromatin landscape, suggesting that these factors serve a pioneering function during Tr1 cell differentiation.

Original language	English (US)
Pages (from-to)	412-421
Number of pages	10
Journal	Nature Immunology
Volume	18
Issue number	4
DOIs	https://doi.org/10.1038/ni.3683
State	Published - Mar 22 2017

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation. / Karwacz, Katarzyna; Miraldi, Emily R.; Pokrovskii, Maria; Madi, Asaf; Yosef, Nir; Wortman, Ivo; Chen, Xi; Watters, Aaron; Carriero, Nicholas; Awasthi, Amit; Regev, Aviv; Bonneau, Richard; Littman, Dan; Kuchroo, Vijay K.

In: Nature Immunology, Vol. 18, No. 4, 22.03.2017, p. 412-421.

Research output: Contribution to journal › Article › peer-review

Karwacz, Katarzyna ; Miraldi, Emily R. ; Pokrovskii, Maria ; Madi, Asaf ; Yosef, Nir ; Wortman, Ivo ; Chen, Xi ; Watters, Aaron ; Carriero, Nicholas ; Awasthi, Amit ; Regev, Aviv ; Bonneau, Richard ; Littman, Dan ; Kuchroo, Vijay K. / Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation. In: Nature Immunology. 2017 ; Vol. 18, No. 4. pp. 412-421.

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title = "Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation",

abstract = "Type 1 regulatory T cells (Tr1 cells) are induced by interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. We found that the transcription factors IRF1 and BATF were induced early on after treatment with IL-27 and were required for the differentiation and function of Tr1 cells in vitro and in vivo. Epigenetic and transcriptional analyses revealed that both transcription factors influenced chromatin accessibility and expression of the genes required for Tr1 cell function. IRF1 and BATF deficiencies uniquely altered the chromatin landscape, suggesting that these factors serve a pioneering function during Tr1 cell differentiation.",

author = "Katarzyna Karwacz and Miraldi, {Emily R.} and Maria Pokrovskii and Asaf Madi and Nir Yosef and Ivo Wortman and Xi Chen and Aaron Watters and Nicholas Carriero and Amit Awasthi and Aviv Regev and Richard Bonneau and Dan Littman and Kuchroo, {Vijay K.}",

note = "Funding Information: This work was supported by the US national Institutes of Health (R01 NS 030843, R01 NS 045937, P01 AI073748, P01 NS076410, P01 AI039671 and 5P01 AI056299-10 to V.K.K.; P01NS076410 to D.L. and M.P.; 5T32AI100853 to M.P.; 1R01-DK103358-01 to E.R.M., R.B. and D.L.; and 1R01-GM112192-01 to R.B.), the National Multiple Sclerosis Society (K.K.), Marie Sklodowska-Curie Actions (of the European Commission / Research Executive Agency), grant agreement number 302915, Marie Curie International Outgoing Fellowship (K.K.), the National Science Foundation (IOS-1126971 to R.B.), the DBT-Wellcome Trust (IA/I/12/1/500524 to A.A.), the Klarman Cell Observatory at the Broad Institute (A.R.), the Howard Hughes Medical Institute (A.R.) and the National Cancer Institute (Koch Institute Support (P30-CA14051 to A.R.).",

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AU - Madi, Asaf

AU - Yosef, Nir

AU - Wortman, Ivo

AU - Chen, Xi

AU - Watters, Aaron

AU - Carriero, Nicholas

AU - Awasthi, Amit

AU - Regev, Aviv

AU - Bonneau, Richard

AU - Littman, Dan

AU - Kuchroo, Vijay K.

N1 - Funding Information: This work was supported by the US national Institutes of Health (R01 NS 030843, R01 NS 045937, P01 AI073748, P01 NS076410, P01 AI039671 and 5P01 AI056299-10 to V.K.K.; P01NS076410 to D.L. and M.P.; 5T32AI100853 to M.P.; 1R01-DK103358-01 to E.R.M., R.B. and D.L.; and 1R01-GM112192-01 to R.B.), the National Multiple Sclerosis Society (K.K.), Marie Sklodowska-Curie Actions (of the European Commission / Research Executive Agency), grant agreement number 302915, Marie Curie International Outgoing Fellowship (K.K.), the National Science Foundation (IOS-1126971 to R.B.), the DBT-Wellcome Trust (IA/I/12/1/500524 to A.A.), the Klarman Cell Observatory at the Broad Institute (A.R.), the Howard Hughes Medical Institute (A.R.) and the National Cancer Institute (Koch Institute Support (P30-CA14051 to A.R.).

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Y1 - 2017/3/22

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