{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:36:48Z","timestamp":1792100208386,"version":"4.4.0"},"reference-count":74,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6644","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2023,5,5]]},"abstract":"<jats:p>The incomplete removal of T cells that are reactive against self-proteins during their differentiation in the thymus requires mechanisms of tolerance that prevent their effector function within the periphery. A further challenge is imposed by the need to establish tolerance to the holobiont self, which comprises a highly complex community of commensal microorganisms. Here, we review recent advances in the investigation of peripheral T cell tolerance, focusing on new insights into mechanisms of tolerance to the gut microbiota, including tolerogenic antigen-presenting cell types and immunomodulatory lymphocytes, and their layered ontogeny that underlies developmental windows for establishing intestinal tolerance. While emphasizing the intestine as a model tissue for studying peripheral T cell tolerance, we highlight overlapping and distinct pathways that underlie tolerance to self-antigens versus commensal antigens within a broader framework for immune tolerance.<\/jats:p>","DOI":"10.1126\/science.adg6425","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T13:59:46Z","timestamp":1683208786000},"page":"472-478","update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":57,"title":["Spatiotemporal regulation of peripheral T cell tolerance"],"prefix":"10.1126","volume":"380","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5834-926X","authenticated-orcid":true,"given":"Chrysothemis C.","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-2898","authenticated-orcid":true,"given":"Alexander Y.","family":"Rudensky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.12.005"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05501-7"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05309-5"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05089-y"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05141-x"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00454-2"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.05.001"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3331"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1907615116"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04524-x"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04916-6"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.10.011"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aaw0902"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00259-X"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160062"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192179"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05432-3"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.001"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0221-9"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01379-9"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.12.001"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09370"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi9591"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf3892"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.01.004"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101235"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa7017"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf3111"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.009"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0280-2"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.05.010"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa9420"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aau9079"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25500"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.092"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg5645"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac4263"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0316-2"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.04.013"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac5560"},{"key":"e_1_3_1_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0461-z"},{"key":"e_1_3_1_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.01.033"},{"key":"e_1_3_1_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abi4613"},{"key":"e_1_3_1_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198469"},{"key":"e_1_3_1_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636751"},{"key":"e_1_3_1_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.09.018"},{"key":"e_1_3_1_48_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070719"},{"key":"e_1_3_1_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1145697"},{"key":"e_1_3_1_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2193-0"},{"key":"e_1_3_1_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1865-0"},{"key":"e_1_3_1_52_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241165"},{"key":"e_1_3_1_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12721"},{"key":"e_1_3_1_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12726"},{"key":"e_1_3_1_55_2","unstructured":"S. Dikiy A. G. Levine Y. Pritykin C. Krishna A. Glasner C. S. Leslie A. Y. Rudensky bioRxiv 2022.05.16.492030 [Preprint] (2003); https:\/\/doi.org\/10.1101\/2022.05.16.492030.10.1101\/2022.05.16.492030"},{"key":"e_1_3_1_56_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141040"},{"key":"e_1_3_1_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-9966-8_1"},{"key":"e_1_3_1_58_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-061020-053707"},{"key":"e_1_3_1_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2370"},{"key":"e_1_3_1_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2134-y"},{"key":"e_1_3_1_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.019"},{"key":"e_1_3_1_62_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12747"},{"key":"e_1_3_1_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.05.025"},{"key":"e_1_3_1_64_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082394"},{"key":"e_1_3_1_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3408"},{"key":"e_1_3_1_66_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160062"},{"key":"e_1_3_1_67_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl5053"},{"key":"e_1_3_1_68_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20181430"},{"key":"e_1_3_1_69_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1159407"},{"key":"e_1_3_1_70_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf1968"},{"key":"e_1_3_1_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01247-6"},{"key":"e_1_3_1_72_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abk2189"},{"key":"e_1_3_1_73_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aao1314"},{"key":"e_1_3_1_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.030"},{"key":"e_1_3_1_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.10.007"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.adg6425","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T18:39:47Z","timestamp":1705343987000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.adg6425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,5]]},"references-count":74,"journal-issue":{"issue":"6644","published-print":{"date-parts":[[2023,5,5]]}},"alternative-id":["10.1126\/science.adg6425"],"URL":"https:\/\/doi.org\/10.1126\/science.adg6425","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,5]]},"assertion":[{"value":"2023-02-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}