| 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)
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