{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:45:31Z","timestamp":1768520731902,"version":"3.49.0"},"posted":{"date-parts":[[2025,3,6]]},"group-title":"Immunology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,6]]},"abstract":"<jats:p>SUMMARY Despite ocular immune privilege, circulating retina-specific T cells can trigger autoimmune uveitis, yet intraocular bleeding-a relatively common event-rarely leads to disease. Using an in vivo immune privilege model, we previously reported that all naive retina-specific T cells entering the eye become primed in situ; about 30% become Foxp3+ T-regulatory cells (Tregs), while the rest fail to induce pathology. Here, single-cell transcriptomics and functional validation revealed distinct phenotypes in both populations: ocular Tregs were highly suppressive, whereas non-Tregs expressed suppression- and anergy-associated genes and lacked regulatory function. Trajectory analyses suggested that Tregs and anergic cells arise from a common proliferative precursor in parallel, rather than sequentially. Our data indicate a key checkpoint governing the divergence of anergic and regulatory fates. These findings provide molecular-level insights into ocular immune privilege and may inform strategies to silence autoimmune effector cells or reverse T cell unresponsiveness in cancer, vaccination, or chronic infection.<\/jats:p>","DOI":"10.1101\/2025.03.01.640701","type":"posted-content","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T07:42:31Z","timestamp":1741333351000},"source":"Crossref","is-referenced-by-count":1,"title":["Ocular immune privilege in action: the living eye imposes unique regulatory and anergic gene signatures on uveitogenic T cells"],"prefix":"10.64898","author":[{"given":"Zixuan","family":"Peng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijayaraj","family":"Nagarajan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reiko","family":"Horai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingyos","family":"Jittayasothorn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary J","family":"Mattapallil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7140-7671","authenticated-orcid":false,"given":"Rachel R","family":"Caspi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.03.01.640701","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:12:22Z","timestamp":1768464742000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.03.01.640701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,6]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1101\/2025.03.01.640701","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.celrep.2025.115780","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,3,6]]},"subtype":"preprint"}}