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Peripherally induced T regulatory (pT\n                    <jats:sub>reg<\/jats:sub>\n                    ) cells are essential for mitigating inflammatory responses to these agents\n                    <jats:sup>1\u20134<\/jats:sup>\n                    . Although ROR\u03b3t\n                    <jats:sup>+<\/jats:sup>\n                    antigen-presenting cells (APCs) have been shown to programme gut microbiota-specific pT\n                    <jats:sub>reg<\/jats:sub>\n                    cells\n                    <jats:sup>5\u20137<\/jats:sup>\n                    , their definition remains incomplete, and the APC responsible for food tolerance has remained unknown. Here we identify an APC subset that is required for differentiation of both food- and microbiota-specific pT\n                    <jats:sub>reg<\/jats:sub>\n                    cells and for establishment of oral tolerance. Development and function of these APCs require expression of the transcription factors PRDM16 and ROR\u03b3t, as well as a unique\n                    <jats:italic>Rorc(t)<\/jats:italic>\n                    <jats:italic>cis<\/jats:italic>\n                    -regulatory element. Gene expression, chromatin accessibility, and surface marker analysis establish the pT\n                    <jats:sub>reg<\/jats:sub>\n                    -inducing APCs as myeloid in origin, distinct from type 3 innate lymphoid cells, and sharing epigenetic profiles with classical dendritic cells, and designate them PRDM16\n                    <jats:sup>+<\/jats:sup>\n                    ROR\u03b3t\n                    <jats:sup>+<\/jats:sup>\n                    tolerizing dendritic cells (tolDCs). Upon genetic perturbation of tolDCs, we observe a substantial increase in food antigen-specific T helper 2 cells in lieu of pT\n                    <jats:sub>reg<\/jats:sub>\n                    cells, leading to compromised tolerance in mouse models of asthma and food allergy. Single-cell analyses of freshly resected mesenteric lymph nodes from a human organ donor, as well as multiple specimens of human intestine and tonsil, reveal candidate tolDCs with co-expression of\n                    <jats:italic>PRDM16<\/jats:italic>\n                    and\n                    <jats:italic>RORC<\/jats:italic>\n                    and an extensive transcriptome shared with tolDCs from mice, highlighting an evolutionarily conserved role across species. Our findings suggest that a better understanding of how tolDCs develop and how they regulate T cell responses to food and microbial antigens could offer new insights into developing therapeutic strategies for autoimmune and allergic diseases as well as organ transplant tolerance.\n                  <\/jats:p>","DOI":"10.1038\/s41586-025-08982-4","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T11:02:22Z","timestamp":1744628542000},"page":"756-765","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["PRDM16-dependent antigen-presenting cells induce tolerance to gut antigens"],"prefix":"10.1038","volume":"642","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4108-3220","authenticated-orcid":false,"given":"Liuhui","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2154-0132","authenticated-orcid":false,"given":"Rabi","family":"Upadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Pokrovskii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6615-4155","authenticated-orcid":false,"given":"Francis M.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Romero-Meza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4894-2024","authenticated-orcid":false,"given":"Adam","family":"Griesemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2850-8688","authenticated-orcid":false,"given":"Dan R.","family":"Littman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"8982_CR1","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1146\/annurev-immunol-020711-075043","volume":"30","author":"AM Bilate","year":"2012","unstructured":"Bilate, A. 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