ArticleThe Journal of experimental medicine2016
IL-1-induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 108 citations in OpenAlex.
- Article
- REV-ERB regulates RORγt+ regulatory T cell specification and function through the Bhlhe40-c-Maf axis.The Journal of experimental medicine · 2026Article
- Is Obesity a Modifiable Risk Factor in Multiple Sclerosis? Mechanistic Insights into Neuroinflammation and Oxidative Damage.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Genomechanical modeling of delayed fracture healing integrating transcriptomics and tissue mechanics.Biomaterials advances · 2026Article
- Tfh2 and a subset of Tfh1 cells associate with antibody-mediated immunity to malaria.JCI insight · 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 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
- Regulatory T cell therapy promotes TGF-β and IL-6-dependent pro-inflammatory Th17 cell generation by reducing IL-2.Nature communications · 2025Article
- Endoscopic healing in pediatric IBD perpetuates a persistent signature defined by Th17 cells with molecular and microbial drivers of disease.Cell reports. Medicine · 2025Article
- BHLHE40 contributes to allergic asthma progression in mice through NRTN downregulation in macrophages.Communications biology · 2025Article
- Histone deacetylases facilitate Th17-cell differentiation and pathogenicity in autoimmune uveitis via CDK6/ID2 axis.Journal of advanced research · 2025Article
- Migration arrest and transendothelial trafficking of human pathogenic-like Th17 cells are mediated by differentially positioned chemokines.Nature communications · 2025Article
- Interaction between Th17 and central nervous system in multiple sclerosis.Brain, behavior, & immunity - health · 2025Review
- 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
- Oleic acid triggers metabolic rewiring of T cells poising them for T helper 9 differentiation.iScience · 2024Article
- Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation.The Journal of experimental medicine · 2024Article
- The emerging role of effector functions exerted by tissue-resident memory T cells.Oxford open immunology · 2024Review
- BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract against Chlamydia.PLoS pathogens · 2024Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
The features that define autoreactive T helper (Th) cell pathogenicity remain obscure. We have previously shown that Th cells require the transcription factor Bhlhe40 to mediate experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Here, using Bhlhe40 reporter mice and analyzing both polyclonal and TCR transgenic Th cells, we found that Bhlhe40 expression was heterogeneous after EAE induction, with Bhlhe40-expressing cells displaying marked production of IFN-γ, IL-17A, and granulocyte-macrophage colony-stimulating factor. In adoptive transfer EAE models, Bhlhe40-deficient Th1 and Th17 cells were both nonencephalitogenic. Pertussis toxin (PTX), a classical co-adjuvant for actively induced EAE, promoted IL-1β production by myeloid cells in the draining lymph node and served as a strong stimulus for Bhlhe40 expression in Th cells. Furthermore, PTX co-adjuvanticity was Bhlhe40 dependent. IL-1β induced Bhlhe40 expression in polarized Th17 cells, and Bhlhe40-expressing cells exhibited an encephalitogenic transcriptional signature. In vivo, IL-1R signaling was required for full Bhlhe40 expression by Th cells after immunization. Overall, we demonstrate that Bhlhe40 expression identifies encephalitogenic Th cells and defines a PTX-IL-1-Bhlhe40 pathway active in EAE.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.