{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T09:31:28Z","timestamp":1786786288543,"version":"build-2736575974"},"reference-count":66,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"790","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,3,19]]},"abstract":"<jats:p>\n            Celiac disease, a gluten-sensitive enteropathy, demonstrates a strong human leukocyte antigen (HLA) association, with more than 90% of patients carrying the HLA-DQ2.5 allotype. No therapy is available for the condition except for a lifelong gluten-free diet. To address this gap, we explored the therapeutic potential of regulatory T cells (T\n            <jats:sub>regs<\/jats:sub>\n            ). By orthotopic replacement of T cell receptors (TCRs) through homology-directed repair, we generated gluten-reactive HLA-DQ2.5\u2013restricted CD4\n            <jats:sup>+<\/jats:sup>\n            engineered (e) T effector cells (T\n            <jats:sub>effs<\/jats:sub>\n            ) and eT\n            <jats:sub>regs<\/jats:sub>\n            and performed in vivo experiments in HLA-DQ2.5 transgenic mice. Of five validated TCRs, TCRs specific for two immunodominant and deamidated gluten epitopes (DQ2.5-glia-\u03b11a and DQ2.5-glia-\u03b12) were selected for further evaluation. CD4\n            <jats:sup>+<\/jats:sup>\n            eT\n            <jats:sub>effs<\/jats:sub>\n            exposed to deamidated gluten through oral gavage colocalized with dendritic and B cells in the Peyer\u2019s patches and gut-draining lymph nodes and specifically migrated to the intestine. The suppressive function of human eT\n            <jats:sub>regs<\/jats:sub>\n            correlated with high TCR functional activity. eT\n            <jats:sub>regs<\/jats:sub>\n            specific for one epitope suppressed the proliferation and gut migration of CD4\n            <jats:sup>+<\/jats:sup>\n            eT\n            <jats:sub>effs<\/jats:sub>\n            specific for the same and the other gluten epitope, demonstrating bystander suppression. The suppression requires an antigen-specific activation of eT\n            <jats:sub>regs<\/jats:sub>\n            given that polyclonal T\n            <jats:sub>regs<\/jats:sub>\n            failed to suppress CD4\n            <jats:sup>+<\/jats:sup>\n            eT\n            <jats:sub>effs<\/jats:sub>\n            . These findings highlight the potential of gluten-reactive eT\n            <jats:sub>regs<\/jats:sub>\n            as a therapeutic for celiac disease.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adr8941","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T17:58:39Z","timestamp":1742407119000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["T cell receptor precision editing of regulatory T cells for celiac disease"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2781-9250","authenticated-orcid":true,"given":"Rapha\u00ebl","family":"Porret","sequence":"first","affiliation":[{"name":"Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9452-6788","authenticated-orcid":true,"given":"Ana","family":"Alcaraz-Serna","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0327-4426","authenticated-orcid":true,"given":"Benjamin","family":"Peter","sequence":"additional","affiliation":[{"name":"Laboratories of Neuroimmunology, Service of Neurology and Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6407-1049","authenticated-orcid":true,"given":"Jeremiah","family":"Bernier-Latmani","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lausanne University Hospital and University of Lausanne, 1005 Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8770-1940","authenticated-orcid":true,"given":"Rebecca","family":"Cecchin","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9963-7137","authenticated-orcid":true,"given":"Oscar","family":"Alfageme-Abello","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3378-1785","authenticated-orcid":true,"given":"Laura","family":"Ermellino","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2494-449X","authenticated-orcid":true,"given":"Morteza","family":"Hafezi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lausanne University Hospital and University of Lausanne, 1005 Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6898-1201","authenticated-orcid":true,"given":"Eleonora","family":"Pace","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Fleur","family":"du Pr\u00e9","sequence":"additional","affiliation":[{"name":"Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo and Department of Immunology, Oslo University Hospital, Oslo NO-0424, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Lana","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5631-6096","authenticated-orcid":true,"given":"Dela","family":"Golshayan","sequence":"additional","affiliation":[{"name":"Transplantation Center, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-5871","authenticated-orcid":true,"given":"Dominique","family":"Velin","sequence":"additional","affiliation":[{"name":"Service of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8262-1190","authenticated-orcid":true,"given":"Justin","family":"Eyquem","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7313-3574","authenticated-orcid":true,"given":"Qizhi","family":"Tang","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-6521","authenticated-orcid":true,"given":"Tatiana V.","family":"Petrova","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lausanne University Hospital and University of Lausanne, 1005 Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8813-7367","authenticated-orcid":true,"given":"George","family":"Coukos","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lausanne University Hospital and University of Lausanne, 1005 Lausanne, Switzerland."},{"name":"Ludwig Institute for Cancer Research Lausanne Branch, 1066 Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6849-7194","authenticated-orcid":true,"given":"Melita","family":"Irving","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lausanne University Hospital and University of Lausanne, 1005 Lausanne, Switzerland."},{"name":"Ludwig Institute for Cancer Research Lausanne Branch, 1066 Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1146-3129","authenticated-orcid":true,"given":"Caroline","family":"Pot","sequence":"additional","affiliation":[{"name":"Laboratories of Neuroimmunology, Service of Neurology and Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3651-2721","authenticated-orcid":true,"given":"Giuseppe","family":"Pantaleo","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8860-704X","authenticated-orcid":true,"given":"Ludvig M.","family":"Sollid","sequence":"additional","affiliation":[{"name":"Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo and Department of Immunology, Oslo University Hospital, Oslo NO-0424, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0513-7156","authenticated-orcid":true,"given":"Yannick D.","family":"Muller","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne CH-1005, Switzerland."},{"name":"Centre for Human Immunology Lausanne, Lausanne CH-1005, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","first-page":"148","article-title":"Celiac disease affects 1% of global population: Who will manage all these patients?","volume":"167","author":"Kurppa K.","year":"2024","unstructured":"K. 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Schmidt M. Weigert C. Broaddus G. Myers Cell detection with star-convex polygons in Medical Image Computing and Computer Assisted Intervention\u2013MICCAI 2018: 21st International Conference Proceedings Part II 11 (Springer 2018) pp. 265\u2013273.","DOI":"10.1007\/978-3-030-00934-2_30"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adr8941","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T17:59:07Z","timestamp":1742407147000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adr8941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":66,"journal-issue":{"issue":"790","published-print":{"date-parts":[[2025,3,19]]}},"alternative-id":["10.1126\/scitranslmed.adr8941"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adr8941","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,19]]},"assertion":[{"value":"2024-07-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadr8941"}}