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Title	en Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-γ production in iNKT cells
Creator	en Kanda, Masatoshi en Yamanaka, Hiroyuki en Kojo, Satoshi NRID 1000070360542 en Usui, Yuu en Honda, Hiroaki NRID 1000040245064 en Sotomaru, Yusuke NRID 1000090309352 en Harada, Michishige en Taniguchi, Masaru NRID 1000080110310 en Suzuki, Nao NRID 1000090246356 en Atsumi, Tatsuya NRID 1000020301905 en Wada, Haruka NRID 1000070392181 en Baghdadi, Muhammad en Seino, Ken-ichiro NRID 1000020312845
Accessrights	open access
Subject	Other en natural killer T cells Other en basic helix-loop-helix transcription factors Other en Bhlhe40 Other ja interferon-γ Other en interferon-gamma Other en T-box transcription factor Tbx21 Other en chromatin NDC 490
Description	Abstract en 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.
Publisher	en National Academy of Sciences
Date	Issued2016-06-14
Language	eng
Resource Type	journal article
Version Type	AM
Identifier	HDL http://hdl.handle.net/2115/63817
Relation	isVersionOf DOI https://doi.org/10.1073/pnas.1604178113
Journal	PISSN 0027-8424 NCID AA10808769 en Proceedings of the National Academy of Sciences of the United States of America Volume Number113 Issue Number24 Page StartE3394 Page EndE3402
File	fulltext PNAS113_E3394-SI.pdf 650.45 KB (application/pdf) Issued2016-06-14 fulltext PNAS113_E3394.pdf 1.66 MB (application/pdf) Issued2016-06-14
Oaidate	2023-07-26