ArticleProceedings of the National Academy of Sciences of the United States of America2016
Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-γ production in iNKT cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- BHLHE40 as a transcriptional rheostat: decoding microenvironmental signals in context-dependent tumor plasticity.Science China. Life sciences · 2026Review
- Endothelial mechanosensitive transcription factor BHLHE40 induced by Piezo1 suppresses endothelial ferroptosis and inflammation via SLC7A11.Cell death discovery · 2025Article
- Optimal CXCR5 expression during Tfh maturation involves the Bhlhe40-Pou2af1 axis.Cell reports · 2025Article
- Multi-omics uncovers transcriptional programs of gut-resident memory CD4+ T cells in Crohn's disease.The Journal of experimental medicine · 2025Article
- BHLHE40 Cooperates with GATA2/3 to Control Human Syncytiotrophoblast Lineage Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Bhlhe40 Coordinates T Cell Programs with Distinct CD4 and CD8 T Cell Requirements for Anti-PD-1 Versus Anti-CTLA-4.bioRxiv : the preprint server for biology · 2025Article
- Innateness transcriptome gradients characterize mouse T lymphocyte populations.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- An Assessment of BHLHE40 Transcription Factor Level and its Target Cytokines in Patients with Rheumatoid Arthritis.Recent advances in inflammation & allergy drug discovery · 2025Article
- Bhlhe40 Promotes CD4+ T Helper 1 Cell and Suppresses T Follicular Helper Cell Differentiation during Viral Infection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Unique adipose tissue invariant natural killer T cell subpopulations control adipocyte turnover in mice.Nature communications · 2023Article
- Bhlhe40 limits early IL-10 production from CD4Infection and immunity · 2023Article
- T-BET and EOMES sustain mature human NK cell identity and antitumor function.The Journal of clinical investigation · 2023Article
- The single-cell transcriptional landscape of innate and adaptive lymphocytes in pediatric-onset colitis.Cell reports. Medicine · 2023Article
- Characterization of Metal-Specific T-Cells in Inflamed Oral Mucosa in a Novel Murine Model of Chromium-Induced Allergic Contact Dermatitis.International journal of molecular sciences · 2023Article
- BHLHE40 Regulates the T-Cell Effector Function Required for Tumor Microenvironment Remodeling and Immune Checkpoint Therapy Efficacy.Cancer immunology research · 2022Article
- Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis.The Journal of experimental medicine · 2022Article
- IFNγ signaling integrity in colorectal cancer immunity and immunotherapy.Cellular & molecular immunology · 2022Review
- BHLHE40 promotes macrophage pro-inflammatory gene expression and functions.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- On Deep Landscape Exploration of COVID-19 Patients Cells and Severity Markers.Frontiers in immunology · 2021Article
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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