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Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-γ production in iNKT cells

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Title: Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-γ production in iNKT cells
Authors: Kanda, Masatoshi Browse this author
Yamanaka, Hiroyuki Browse this author
Kojo, Satoshi Browse this author →KAKEN DB
Usui, Yuu Browse this author
Honda, Hiroaki Browse this author →KAKEN DB
Sotomaru, Yusuke Browse this author →KAKEN DB
Harada, Michishige Browse this author
Taniguchi, Masaru Browse this author →KAKEN DB
Suzuki, Nao Browse this author →KAKEN DB
Atsumi, Tatsuya Browse this author →KAKEN DB
Wada, Haruka Browse this author →KAKEN DB
Baghdadi, Muhammad Browse this author
Seino, Ken-ichiro Browse this author →KAKEN DB
Keywords: natural killer T cells
basic helix-loop-helix transcription factors
Bhlhe40
interferon-γ
interferon-gamma
T-box transcription factor Tbx21
chromatin
Issue Date: 14-Jun-2016
Publisher: National Academy of Sciences
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 113
Issue: 24
Start Page: E3394
End Page: E3402
Publisher DOI: 10.1073/pnas.1604178113
Abstract: Invariant natural killer T (iNKT) cells are a subset of innate-like T cells that act as important mediators of immune responses. In particular, iNKT cells have the ability to immediately produce large amounts of IFN-γ upon activation and thus initiate immune responses in various pathological conditions. However, molecular mechanisms that control IFN-γ production in iNKT cells are not fully understood. Here, we report that basic helix-loop-helix transcription factor family, member e40 (Bhlhe40), is an important regulator for IFN-γ production in iNKT cells. Bhlhe40 is highly expressed in stage 3 thymic iNKT cells and iNKT1 subsets, and the level of Bhlhe40 mRNA expression is correlated with Ifng mRNA expression in the resting state. Although Bhlhe40-deficient mice show normal iNKT cell development, Bhlhe40-deficient iNKT cells show significant impairment of IFN-γ production and antitumor effects. Bhlhe40 alone shows no significant effects on Ifng promoter activities but contributes to enhance T-box transcription factor Tbx21 (T-bet)-mediated Ifng promoter activation. Chromatin immunoprecipitation analysis revealed that Bhlhe40 accumulates in the T-box region of the Ifng locus and contributes to histone H3-lysine 9 acetylation of the Ifng locus, which is impaired without T-bet conditions. These results indicate that Bhlhe40 works as a cofactor of T-bet for enhancing IFN-γ production in iNKT cells.
Type: article (author version)
URI: http://hdl.handle.net/2115/63817
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 清野 研一郎

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