RRC ID |
64931
|
著者 |
Kanda M, Yamanaka H, Kojo S, Usui Y, Honda H, Sotomaru Y, Harada M, Taniguchi M, Suzuki N, Atsumi T, Wada H, Baghdadi M, Seino K.
|
タイトル |
Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-γ production in iNKT cells.
|
ジャーナル |
Proc Natl Acad Sci U S A
|
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.
|
巻・号 |
113(24)
|
ページ |
E3394-402
|
公開日 |
2016-6-14
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DOI |
10.1073/pnas.1604178113
|
PII |
1604178113
|
PMID |
27226296
|
PMC |
PMC4914147
|
MeSH |
Animals
Basic Helix-Loop-Helix Transcription Factors / genetics
Basic Helix-Loop-Helix Transcription Factors / immunology*
Gene Expression Regulation / genetics
Gene Expression Regulation / immunology*
Homeodomain Proteins / genetics
Homeodomain Proteins / immunology*
Immunity, Cellular / genetics
Interferon-gamma / genetics
Interferon-gamma / immunology*
Mice
Mice, Knockout
Natural Killer T-Cells / immunology*
Neoplasms, Experimental / genetics
Neoplasms, Experimental / immunology
Promoter Regions, Genetic / immunology*
T-Box Domain Proteins / genetics
T-Box Domain Proteins / immunology*
|
IF |
9.412
|
リソース情報 |
ヒト・動物細胞 |
EL4(RCB1641) |