ArticleThe Journal of experimental medicine2026
Oral antigen exposure under costimulation blockade induces Treg cells to establish immune tolerance.
Article in The Journal of experimental medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Causal Relationships Between Oral Microbiota and Inflammatory Skin Diseases.International dental journal · 2026Article
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- B7 costimulation antagonizes RORγt+ regulatory T cells and immune tolerance in the intestine.The Journal of experimental medicine · 2026Article
- Human epidermal resident memory T cells: beyond the dermal perspective.Frontiers in immunology · 2026Review
- The relativity of regulatory T cell suppression modes.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Antigen-specific oral tolerance prevents harmful immune responses in naïve animals but is difficult to induce in antigen-primed hosts. Here, we showed that feeding of antigen-containing diet generated peripherally derived regulatory T (pTreg) cells with tissue-adapted effector properties. They acquired Treg-specific epigenomic changes at Treg signature genes, including Foxp3, exhibiting stable suppressive function. Cessation of antigen feeding diminished pTreg cells, hampering tolerance induction. Notably, pTreg cells induced by antigen feeding predominantly expressed CD101. CD101+ Treg cells with similar phenotypic and epigenetic features could also be generated in vitro from antigen-primed naïve CD4+ T cells by blocking CD28-mediated costimulation during TGF-β-dependent Treg induction. Furthermore, in mice already antigen-sensitized by nonoral routes, in vivo blockade of CD28 signaling with CTLA4-Ig prior to antigen feeding promoted differentiation of antigen-specific T cells into CD101+ pTreg cells, facilitating oral tolerance. Thus, continuous oral antigen exposure combined with CD28 blockade generates functionally stable CD101+ pTreg cells, thereby establishing systemic antigen-specific tolerance even in antigen-presensitized hosts.
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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.