Batf is important for IL-4 expression in T follicular helper cells

Anupama Sahoo; Andrei Alekseev; Kentaro Tanaka; Lidiya Obertas; Beatrisa Lerman; Cara Haymaker; Karen Clise-Dwyer; John S. McMurray; Roza Nurieva

doi:10.1038/ncomms8997

Batf is important for IL-4 expression in T follicular helper cells

Anupama Sahoo, Andrei Alekseev, Kentaro Tanaka, Lidiya Obertas, Beatrisa Lerman, Cara Haymaker, Karen Clise-Dwyer, John S. McMurray, Roza Nurieva

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

71 Citations (Scopus)

Abstract

Apart from T helper (Th)-2 cells, T follicular helper (Tfh) cells are a major class of IL-4-producing T cells, required for regulation of type 2 humoral immunity; however, transcriptional control of IL-4 production in Tfh cells remains mainly unknown. Here, we show that the basic leucine zipper transcription factor ATF-like, Batf is important for IL-4 expression in Tfh cells rather than in canonical Th2 cells. Functionally, Batf in cooperation with interferon regulatory factor (IRF) 4 along with Stat3 and Stat6 trigger IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region in the IL-4 locus. In addition, Batf-to-c-Maf signalling is an important determinant of IL-4 expression in Tfh cells. Batf deficiency impairs the generation of IL-4-producing Tfh cells that results in protection against allergic asthma. Our results thus indicate a positive role of Batf in promoting the generation of pro-allergic IL-4-producing Tfh cells.

Original language	English
Article number	7997
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8997
Publication status	Published - Aug 17 2015
Externally published	Yes

All Science Journal Classification (ASJC) codes

General
Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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title = "Batf is important for IL-4 expression in T follicular helper cells",

abstract = "Apart from T helper (Th)-2 cells, T follicular helper (Tfh) cells are a major class of IL-4-producing T cells, required for regulation of type 2 humoral immunity; however, transcriptional control of IL-4 production in Tfh cells remains mainly unknown. Here, we show that the basic leucine zipper transcription factor ATF-like, Batf is important for IL-4 expression in Tfh cells rather than in canonical Th2 cells. Functionally, Batf in cooperation with interferon regulatory factor (IRF) 4 along with Stat3 and Stat6 trigger IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region in the IL-4 locus. In addition, Batf-to-c-Maf signalling is an important determinant of IL-4 expression in Tfh cells. Batf deficiency impairs the generation of IL-4-producing Tfh cells that results in protection against allergic asthma. Our results thus indicate a positive role of Batf in promoting the generation of pro-allergic IL-4-producing Tfh cells.",

author = "Anupama Sahoo and Andrei Alekseev and Kentaro Tanaka and Lidiya Obertas and Beatrisa Lerman and Cara Haymaker and Karen Clise-Dwyer and McMurray, {John S.} and Roza Nurieva",

note = "Funding Information: We thank Mark R. Boothby, Vanderbilt University Medical Center for the Stat6 construct. We also thank the South Campus Flow Cytometry and Cell Sorting Core Laboratory, MD Anderson Cancer Center for assistance. This work was supported by an Institutional Research Grant (R.N.), start-up grant (R.N.), MD Anderson CIC seed grant (R.N.), American Asthma Foundation, grant #11–0360 (J.S.M) and in part by the NIH P30 CA16672 funding of the South Campus Flow Cytometry and Cell Sorting Core Laboratory. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",

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doi = "10.1038/ncomms8997",

language = "English",

volume = "6",

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AU - Sahoo, Anupama

AU - Alekseev, Andrei

AU - Tanaka, Kentaro

AU - Obertas, Lidiya

AU - Lerman, Beatrisa

AU - Haymaker, Cara

AU - Clise-Dwyer, Karen

AU - McMurray, John S.

AU - Nurieva, Roza

N1 - Funding Information: We thank Mark R. Boothby, Vanderbilt University Medical Center for the Stat6 construct. We also thank the South Campus Flow Cytometry and Cell Sorting Core Laboratory, MD Anderson Cancer Center for assistance. This work was supported by an Institutional Research Grant (R.N.), start-up grant (R.N.), MD Anderson CIC seed grant (R.N.), American Asthma Foundation, grant #11–0360 (J.S.M) and in part by the NIH P30 CA16672 funding of the South Campus Flow Cytometry and Cell Sorting Core Laboratory. Publisher Copyright: © 2015 Macmillan Publishers Limited. All rights reserved.

PY - 2015/8/17

Y1 - 2015/8/17

N2 - Apart from T helper (Th)-2 cells, T follicular helper (Tfh) cells are a major class of IL-4-producing T cells, required for regulation of type 2 humoral immunity; however, transcriptional control of IL-4 production in Tfh cells remains mainly unknown. Here, we show that the basic leucine zipper transcription factor ATF-like, Batf is important for IL-4 expression in Tfh cells rather than in canonical Th2 cells. Functionally, Batf in cooperation with interferon regulatory factor (IRF) 4 along with Stat3 and Stat6 trigger IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region in the IL-4 locus. In addition, Batf-to-c-Maf signalling is an important determinant of IL-4 expression in Tfh cells. Batf deficiency impairs the generation of IL-4-producing Tfh cells that results in protection against allergic asthma. Our results thus indicate a positive role of Batf in promoting the generation of pro-allergic IL-4-producing Tfh cells.

AB - Apart from T helper (Th)-2 cells, T follicular helper (Tfh) cells are a major class of IL-4-producing T cells, required for regulation of type 2 humoral immunity; however, transcriptional control of IL-4 production in Tfh cells remains mainly unknown. Here, we show that the basic leucine zipper transcription factor ATF-like, Batf is important for IL-4 expression in Tfh cells rather than in canonical Th2 cells. Functionally, Batf in cooperation with interferon regulatory factor (IRF) 4 along with Stat3 and Stat6 trigger IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region in the IL-4 locus. In addition, Batf-to-c-Maf signalling is an important determinant of IL-4 expression in Tfh cells. Batf deficiency impairs the generation of IL-4-producing Tfh cells that results in protection against allergic asthma. Our results thus indicate a positive role of Batf in promoting the generation of pro-allergic IL-4-producing Tfh cells.

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Batf is important for IL-4 expression in T follicular helper cells

Abstract

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