ArticleThe Journal of experimental medicine2025
RORγt eTACs mediate oral tolerance and Treg induction.
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Article
- Article
- Runx-CBFβ regulates the development of tolerogenic Thetis cells.Nature immunology · 2026Article
- B7 costimulation antagonizes RORγt+ regulatory T cells and immune tolerance in the intestine.The Journal of experimental medicine · 2026Article
- Article
- The development of innate lymphoid cells.Nature immunology · 2026Review
- The conserved noncoding sequence CNS11 is a master control region forScience advances · 2026Article
- RORγtScience immunology · 2026Article
- AIRE transcriptional condensates in central tolerance: a multiscale mechanistic perspective.Frontiers in immunology · 2026Review
- Specialized Dendritic Cells Mediating Peripheral Tolerance to Intestinal Antigens.Immunological reviews · 2026Review
- Striking a balance: how the gut microbiome shapes the fate of intestinal CD4+ T cells.Discovery immunology · 2026Review
- Diet Components, Immune Function and IgE-Mediated Food Allergy.Nutrients · 2025Review
- Dendritic Cells: Orchestrators of Immune Responsiveness and Tolerance.Immunological reviews · 2025Review
- Microbiota-mediated mechanisms of mucosal immunity across the lifespan.Nature immunology · 2025Review
- Crosstalk between the microbiota and intestinal dendritic cells in IBD.Seminars in immunopathology · 2025Review
- Thetis cells: regulators of intestinal immune tolerance.Current opinion in immunology · 2025Review
- RORγt-APCs: The New Masters of Oral Tolerance.Barrier immunity · 2025Article
- Emerging diagnostic and therapeutic opportunities in food allergy.Frontiers in immunology · 2025Review
- High Fat and Sugar Diet Increases Enteric cDC1 and Oral Antigen-Specific Tregs.Journal of immunology research · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
The immune system must distinguish pathogens from innocuous dietary antigens, but the precise mechanisms and cellular actors remain unclear. Here, we demonstrate that RORγt-lineage APCs are required for oral tolerance. Using lineage tracing and single-cell sequencing, we show these APCs consist of three principal populations: type 3 innate lymphoid cells (ILC3s), RORγt-lineage dendritic cells, and cells expressing Aire called RORγt eTACs (R-eTACs)-also known as Janus or Thetis cells. We show that R-eTACs, but not ILC3s, are required for oral tolerance induction. We find R-eTACs are of probable myeloid origin and uniquely express integrin β8 (Itgb8). Both MHCII and Itgb8 expression in RORγt-lineage cells are necessary to induce food-specific regulatory T cells. Mice lacking R-eTACs or with deletion of MHCII or Itgb8 in the RORγt lineage fail to generate Tregs and instead develop a T-follicular helper response with elevated antigen-specific antibodies. These findings establish R-eTACs as critical mediators of oral tolerance and suggest novel cellular targets to modulate immune tolerance.
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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.