| First Author | Kanda M | Year | 2016 |
| Journal | Proc Natl Acad Sci U S A | Volume | 113 |
| Issue | 24 | Pages | E3394-402 |
| PubMed ID | 27226296 | Mgi Jnum | J:234104 |
| Mgi Id | MGI:5789068 | Doi | 10.1073/pnas.1604178113 |
| Citation | Kanda M, et al. (2016) Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-gamma production in iNKT cells. Proc Natl Acad Sci U S A 113(24):E3394-402 |
| abstractText | 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-gamma upon activation and thus initiate immune responses in various pathological conditions. However, molecular mechanisms that control IFN-gamma 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-gamma 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-gamma 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-gamma production in iNKT cells. |
