{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:00:34Z","timestamp":1792821634071,"version":"4.5.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Oxfordshire Health Services Research Committee","award":["1396"],"award-info":[{"award-number":["1396"]}]},{"DOI":"10.13039\/100016580","name":"Kennedy Trust for Rheumatology Research","doi-asserted-by":"publisher","award":["KENN202101"],"award-info":[{"award-number":["KENN202101"]}],"id":[{"id":"10.13039\/100016580","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005565","name":"Johnson & Johnson Innovative Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005565","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012618","name":"National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology","doi-asserted-by":"publisher","award":["BRC4-03-RB414-405"],"award-info":[{"award-number":["BRC4-03-RB414-405"]}],"id":[{"id":"10.13039\/501100012618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["22252"],"award-info":[{"award-number":["22252"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Arthritis Therapy Acceleration Programme"},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T024682\/1"],"award-info":[{"award-number":["MR\/T024682\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The current concept is that the eye is an immune privileged site endowed with innate immune regulatory networks to maintain organ function. We now have evidence that resident T cells occupy intraocular tissues. In immune-mediated inflammatory diseases, such as psoriasis and rheumatoid arthritis, tissue resident T cells trigger disease flares in the skin and joints. This suggests resident T cells in the uvea may have similar functions in non-infectious immune-mediated uveitis, a collective term for autoinflammatory and autoimmune diseases of the uveal tract causing intraocular inflammation. Here, we demonstrate by spectral cytometry and immunofluorescence imaging that non-inflamed uveal tissue contains multiple T cell subtypes including CD8\n                    <jats:sup>+<\/jats:sup>\n                    \u2009CD103\n                    <jats:sup>+<\/jats:sup>\n                    \u2009tissue resident memory T (T\n                    <jats:sub>RM<\/jats:sub>\n                    ) cells. Using single cell RNA &amp; T cell receptor (TCR) sequencing to profile aqueous humour cells from donors with acute, active uveitis, we identify clonally expanded T cells which are enriched for T\n                    <jats:sub>RM<\/jats:sub>\n                    -associated genes. We further show that in donors with active uveitis, CD8\n                    <jats:sup>+<\/jats:sup>\n                    \u2009CD103\n                    <jats:sup>+<\/jats:sup>\n                    \u2009T cells persist within tissue in the uveal tract. Using bulk RNA sequencing and weighted gene co-expression network analysis (WGCNA) we show that quiescent iris tissue from donors with a history of uveitis are enriched for genes associated with T cell activation and antigen presentation. Finally, we demonstrate that T\n                    <jats:sub>RM<\/jats:sub>\n                    cells persist in the anterior uvea in mice following resolution of experimental autoimmune uveoretinitis (EAU). Our results show that the human eye contains T cells both in health and during active inflammation. Our findings challenge the dogma that the eye is devoid of lymphocytes and supports the concept of resident T cell involvement in the pathogenesis of non-infectious immune-mediated uveitis and as promising targets for therapy.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-33444-2","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T09:01:40Z","timestamp":1775206900000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tissue resident memory T cells populate the human uveal tract"],"prefix":"10.1038","volume":"16","author":[{"given":"Andrew D.","family":"Foers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.","family":"Reekie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshanie C.","family":"Wickramasinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas MW.","family":"Buckley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moustafa","family":"Attar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soledad","family":"Aguilar-Munoa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Queen","family":"Pilapil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maram EA. Abdalla","family":"Elsayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Pledger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananya","family":"Bhalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hedley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan","family":"Windell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Barton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Masood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin Sheng","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Coles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Sherlock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Dick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Coupland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen N.","family":"Sansom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Copland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Buckley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srilakshmi M.","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"ORBIT Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin J.","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Foers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.","family":"Reekie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshanie C.","family":"Wickramasinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hedley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Sherlock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Dick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Coupland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Copland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Buckley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srilakshmi M.","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"33444_CR1","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1038\/eye.2008.382","volume":"23","author":"AW Taylor","year":"2009","unstructured":"Taylor, A. W. Ocular immune privilege. Eye 23, 1885\u20131889. https:\/\/doi.org\/10.1038\/eye.2008.382 (2009).","journal-title":"Eye"},{"key":"33444_CR2","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1038\/nri1224","volume":"3","author":"JW Streilein","year":"2003","unstructured":"Streilein, J. W. Ocular immune privilege: Therapeutic opportunities from an experiment of nature. Nat. Rev. Immunol. 3, 879\u2013889. https:\/\/doi.org\/10.1038\/nri1224 (2003).","journal-title":"Nat. Rev. Immunol."},{"key":"33444_CR3","doi-asserted-by":"publisher","first-page":"338","DOI":"10.3389\/fimmu.2012.00338","volume":"3","author":"J Forrester","year":"2012","unstructured":"Forrester, J. & Xu, H. Good news\u2013bad news: The Yin and Yang of immune privilege in the eye. Front. Immunol. 3, 338. https:\/\/doi.org\/10.3389\/fimmu.2012.00338 (2012).","journal-title":"Front. Immunol."},{"key":"33444_CR4","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1159\/000099279","volume":"92","author":"J Hori","year":"2007","unstructured":"Hori, J. & Niederkorn, J. Y. Immunogenicity and immune privilege of corneal allografts. Immune Response Eye 92, 290\u2013299 (2007).","journal-title":"Immune Response Eye"},{"key":"33444_CR5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2217795120","volume":"120","author":"LE Downie","year":"2023","unstructured":"Downie, L. E. et al. Redefining the human corneal immune compartment using dynamic intravital imaging. Proc. Natl. Acad. Sci. 120, e2217795120. https:\/\/doi.org\/10.1073\/pnas.2217795120 (2023).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"33444_CR6","doi-asserted-by":"publisher","unstructured":"Hedley, R. et al. IL-23 drives uveitis by acting on a population of tissue-resident entheseal T cells. JCI Insight 10, https:\/\/doi.org\/10.1172\/jci.insight.182616 (2025).","DOI":"10.1172\/jci.insight.182616"},{"key":"33444_CR7","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/s41586-024-07130-8","volume":"628","author":"X Yin","year":"2024","unstructured":"Yin, X. et al. Compartmentalized ocular lymphatic system mediates eye\u2013brain immunity. Nature 628, 204\u2013211. https:\/\/doi.org\/10.1038\/s41586-024-07130-8 (2024).","journal-title":"Nature"},{"key":"33444_CR8","doi-asserted-by":"publisher","first-page":"269rv261","DOI":"10.1126\/scitranslmed.3010641","volume":"7","author":"RA Clark","year":"2015","unstructured":"Clark, R. A. Resident memory T cells in human health and disease. Sci. Trans. Med. 7, 269rv261-269rv261. https:\/\/doi.org\/10.1126\/scitranslmed.3010641 (2015).","journal-title":"Sci. Trans. Med."},{"key":"33444_CR9","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nri.2015.3","volume":"16","author":"SN Mueller","year":"2016","unstructured":"Mueller, S. N. & Mackay, L. K. Tissue-resident memory T cells: local specialists in immune defence. Nat. Rev. Immunol. 16, 79\u201389. https:\/\/doi.org\/10.1038\/nri.2015.3 (2016).","journal-title":"Nat. Rev. Immunol."},{"key":"33444_CR10","doi-asserted-by":"publisher","first-page":"4593","DOI":"10.1038\/s41467-018-07053-9","volume":"9","author":"J Smolders","year":"2018","unstructured":"Smolders, J. et al. Tissue-resident memory T cells populate the human brain. Nat. Commun. 9, 4593. https:\/\/doi.org\/10.1038\/s41467-018-07053-9 (2018).","journal-title":"Nat. Commun."},{"key":"33444_CR11","doi-asserted-by":"publisher","first-page":"e200172","DOI":"10.1212\/NXI.0000000000200172","volume":"11","author":"K Kimitoshi","year":"2024","unstructured":"Kimitoshi, K. et al. Resident memory-like CD8+ T cells are involved in chronic inflammatory and neurodegenerative diseases in the CNS. Neurol. Neuroimmunol. Neuroinflammation 11, e200172. https:\/\/doi.org\/10.1212\/NXI.0000000000200172 (2024).","journal-title":"Neurol. Neuroimmunol. Neuroinflammation"},{"key":"33444_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110852","author":"JK Loi","year":"2022","unstructured":"Loi, J. K. et al. Corneal tissue-resident memory T cells form a unique immune compartment at the ocular surface. Cell Rep. https:\/\/doi.org\/10.1016\/j.celrep.2022.110852 (2022).","journal-title":"Cell Rep."},{"key":"33444_CR13","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/nm.2817","volume":"18","author":"JP Sherlock","year":"2012","unstructured":"Sherlock, J. P. et al. IL-23 induces spondyloarthropathy by acting on ROR-\u03b3t+ CD3+CD4\u2212CD8\u2212 entheseal resident T cells. Nat. Med. 18, 1069\u20131076 (2012).","journal-title":"Nat. Med."},{"key":"33444_CR14","doi-asserted-by":"publisher","first-page":"2476","DOI":"10.1002\/art.39732","volume":"68","author":"A Reinhardt","year":"2016","unstructured":"Reinhardt, A. et al. Interleukin-23\u2013dependent \u03b3\/\u03b4 T cells produce interleukin-17 and accumulate in the enthesis, aortic valve, and ciliary body in mice. Arthr. Rheumatol. 68, 2476\u20132486. https:\/\/doi.org\/10.1002\/art.39732 (2016).","journal-title":"Arthr. Rheumatol."},{"key":"33444_CR15","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.immuni.2017.01.009","volume":"46","author":"S Cheuk","year":"2017","unstructured":"Cheuk, S. et al. CD49a expression defines tissue-resident CD8+ T cells poised for cytotoxic function in human skin. Immunity 46, 287\u2013300. https:\/\/doi.org\/10.1016\/j.immuni.2017.01.009 (2017).","journal-title":"Immunity"},{"key":"33444_CR16","doi-asserted-by":"publisher","first-page":"e67396","DOI":"10.7554\/eLife.67396","volume":"10","author":"M Kasper","year":"2021","unstructured":"Kasper, M. et al. Intraocular dendritic cells characterize HLA-B27-associated acute anterior uveitis. Elife 10, e67396. https:\/\/doi.org\/10.7554\/eLife.67396 (2021).","journal-title":"Elife"},{"key":"33444_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2022.102901","volume":"133","author":"K Deschler","year":"2022","unstructured":"Deschler, K. et al. Antigen-specific immune reactions by expanded CD8+ T cell clones from HLA-B*27-positive patients with spondyloarthritis. J. Autoimmun. 133, 102901. https:\/\/doi.org\/10.1016\/j.jaut.2022.102901 (2022).","journal-title":"J. Autoimmun."},{"key":"33444_CR18","doi-asserted-by":"publisher","first-page":"5675","DOI":"10.1038\/s41467-021-25968-8","volume":"12","author":"P Gautam","year":"2021","unstructured":"Gautam, P. et al. Multi-species single-cell transcriptomic analysis of ocular compartment regulons. Nat. Commun. 12, 5675. https:\/\/doi.org\/10.1038\/s41467-021-25968-8 (2021).","journal-title":"Nat. Commun."},{"key":"33444_CR19","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/j.autrev.2013.04.001","volume":"12","author":"G Wildner","year":"2013","unstructured":"Wildner, G. & Kaufmann, U. What causes relapses of autoimmune diseases? The etiological role of autoreactive T cells. Autoimmun. Rev. 12, 1070\u20131075. https:\/\/doi.org\/10.1016\/j.autrev.2013.04.001 (2013).","journal-title":"Autoimmun. Rev."},{"key":"33444_CR20","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/imm.12503","volume":"146","author":"J Boldison","year":"2015","unstructured":"Boldison, J. et al. A novel pathogenic RBP-3 peptide reveals epitope spreading in persistent experimental autoimmune uveoretinitis. Immunology 146, 301\u2013311. https:\/\/doi.org\/10.1111\/imm.12503 (2015).","journal-title":"Immunology"},{"key":"33444_CR21","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s00011-020-01320-6","volume":"69","author":"S Khalil","year":"2020","unstructured":"Khalil, S., Bardawil, T., Kurban, M. & Abbas, O. Tissue-resident memory T cells in the skin. Inflamm. Res. 69, 245\u2013254. https:\/\/doi.org\/10.1007\/s00011-020-01320-6 (2020).","journal-title":"Inflamm. Res."},{"key":"33444_CR22","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.3389\/fimmu.2020.618897","volume":"11","author":"Y Tokura","year":"2021","unstructured":"Tokura, Y., Phadungsaksawasdi, P., Kurihara, K., Fujiyama, T. & Honda, T. Pathophysiology of skin resident Memory T cells. Front. Immunol. 11, 2020. https:\/\/doi.org\/10.3389\/fimmu.2020.618897 (2021).","journal-title":"Front. Immunol."},{"key":"33444_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.608377","author":"C M\u00f6lzer","year":"2021","unstructured":"M\u00f6lzer, C., Heissigerova, J., Wilson, H. M., Kuffova, L. & Forrester, J. V. Immune privilege: The microbiome and uveitis. Front. Immunol. https:\/\/doi.org\/10.3389\/fimmu.2020.608377 (2021).","journal-title":"Front. Immunol."},{"key":"33444_CR24","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1038\/s41583-018-0070-8","volume":"19","author":"JV Forrester","year":"2018","unstructured":"Forrester, J. V., McMenamin, P. G. & Dando, S. J. CNS infection and immune privilege. Nat. Rev. Neurosci. 19, 655\u2013671. https:\/\/doi.org\/10.1038\/s41583-018-0070-8 (2018).","journal-title":"Nat. Rev. Neurosci."},{"key":"33444_CR25","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.preteyeres.2018.12.002","volume":"70","author":"PG McMenamin","year":"2019","unstructured":"McMenamin, P. G., Saban, D. R. & Dando, S. J. Immune cells in the retina and choroid: Two different tissue environments that require different defenses and surveillance. Prog. Retin. Eye Res. 70, 85\u201398. https:\/\/doi.org\/10.1016\/j.preteyeres.2018.12.002 (2019).","journal-title":"Prog. Retin. Eye Res."},{"key":"33444_CR26","volume-title":"The eye","author":"JV Forrester","year":"2021","unstructured":"Forrester, J. V., Dick, A. D., McMenamin, P., Roberts, F. & Pearlman, E. The eye (Elsevier, Amsterdam, 2021)."},{"key":"33444_CR27","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/nri3391","volume":"13","author":"R Shechter","year":"2013","unstructured":"Shechter, R., London, A. & Schwartz, M. Orchestrated leukocyte recruitment to immune-privileged sites: Absolute barriers versus educational gates. Nat. Rev. Immunol. 13, 206\u2013218. https:\/\/doi.org\/10.1038\/nri3391 (2013).","journal-title":"Nat. Rev. Immunol."},{"key":"33444_CR28","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1038\/s41590-020-0711-8","volume":"21","author":"SL Urban","year":"2020","unstructured":"Urban, S. L. et al. Peripherally induced brain tissue\u2013resident memory CD8+ T cells mediate protection against CNS infection. Nat. Immunol. 21, 938\u2013949. https:\/\/doi.org\/10.1038\/s41590-020-0711-8 (2020).","journal-title":"Nat. Immunol."},{"key":"33444_CR29","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1007\/s00281-022-00934-8","volume":"44","author":"D Y\u00fczen","year":"2022","unstructured":"Y\u00fczen, D., Arck, P. C. & Thiele, K. Tissue-resident immunity in the female and male reproductive tract. Seminars Immunopathol. 44, 785\u2013799. https:\/\/doi.org\/10.1007\/s00281-022-00934-8 (2022).","journal-title":"Seminars Immunopathol."},{"key":"33444_CR30","doi-asserted-by":"publisher","first-page":"4541","DOI":"10.4049\/jimmunol.1301390","volume":"192","author":"J Boldison","year":"2014","unstructured":"Boldison, J. et al. Tissue-resident exhausted effector memory CD8+ T cells accumulate in the retina during chronic experimental autoimmune uveoretinitis. J. Immunol. 192, 4541\u20134550. https:\/\/doi.org\/10.4049\/jimmunol.1301390 (2014).","journal-title":"J. Immunol."},{"key":"33444_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109902","author":"MH Chang","year":"2021","unstructured":"Chang, M. H. et al. Arthritis flares mediated by tissue-resident memory T cells in the joint. Cell Rep. https:\/\/doi.org\/10.1016\/j.celrep.2021.109902 (2021).","journal-title":"Cell Rep."},{"key":"33444_CR32","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1177\/24755303221127338","volume":"7","author":"A Blauvelt","year":"2022","unstructured":"Blauvelt, A. Resident memory T cells in psoriasis: key to a cure?. J. Psoriasis Psoriatic Arthr. 7, 157\u2013159. https:\/\/doi.org\/10.1177\/24755303221127338 (2022).","journal-title":"J. Psoriasis Psoriatic Arthr."},{"key":"33444_CR33","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41572-020-0160-6","volume":"6","author":"M Ramos-Casals","year":"2020","unstructured":"Ramos-Casals, M. et al. Immune-related adverse events of checkpoint inhibitors. Nat. Rev. Dis. Primers. 6, 38. https:\/\/doi.org\/10.1038\/s41572-020-0160-6 (2020).","journal-title":"Nat. Rev. Dis. Primers."},{"key":"33444_CR34","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.ejca.2017.12.008","volume":"91","author":"F-X Danlos","year":"2018","unstructured":"Danlos, F.-X. et al. Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease. Eur. J. Cancer 91, 21\u201329. https:\/\/doi.org\/10.1016\/j.ejca.2017.12.008 (2018).","journal-title":"Eur. J. Cancer"},{"key":"33444_CR35","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/s41584-022-00841-0","volume":"18","author":"A Tison","year":"2022","unstructured":"Tison, A., Garaud, S., Chiche, L., Cornec, D. & Kostine, M. Immune-checkpoint inhibitor use in patients with cancer and pre-existing autoimmune diseases. Nat. Rev. Rheumatol. 18, 641\u2013656. https:\/\/doi.org\/10.1038\/s41584-022-00841-0 (2022).","journal-title":"Nat. Rev. Rheumatol."},{"issue":"6","key":"33444_CR36","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1097\/IAE.0000000000002181","volume":"38","author":"LA Dalvin","year":"2018","unstructured":"Dalvin, L. A., Shields, C. L., Orloff, M., Sato, T. & Shields, J. A. CHECKPOINT INHIBITOR IMMUNE THERAPY: systemic indications and ophthalmic side effects. Retina 38(6), 1063\u20131078 (2018).","journal-title":"Retina"},{"key":"33444_CR37","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1146\/annurev-immunol-093019-112809","volume":"40","author":"JI Gray","year":"2022","unstructured":"Gray, J. I. & Farber, D. L. Tissue-resident immune cells in humans. Annu. Rev. Immunol. 40, 195\u2013220. https:\/\/doi.org\/10.1146\/annurev-immunol-093019-112809 (2022).","journal-title":"Annu. Rev. Immunol."},{"key":"33444_CR38","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1053\/j.gastro.2021.06.025","volume":"161","author":"SC Sasson","year":"2021","unstructured":"Sasson, S. C. et al. Interferon-gamma\u2013producing CD8+ tissue resident memory T cells are a targetable hallmark of immune checkpoint inhibitor-colitis. Gastroenterology 161, 1229-1244.e1229. https:\/\/doi.org\/10.1053\/j.gastro.2021.06.025 (2021).","journal-title":"Gastroenterology"},{"key":"33444_CR39","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.cell.2020.06.001","volume":"182","author":"AM Luoma","year":"2020","unstructured":"Luoma, A. M. et al. Molecular pathways of colon inflammation induced by cancer immunotherapy. Cell 182, 655-671.e622. https:\/\/doi.org\/10.1016\/j.cell.2020.06.001 (2020).","journal-title":"Cell"},{"key":"33444_CR40","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1158\/2326-6066.CIR-22-0362","volume":"10","author":"R Reschke","year":"2022","unstructured":"Reschke, R. et al. Checkpoint blockade-induced dermatitis and colitis are dominated by tissue-resident memory T cells and Th1\/Tc1 cytokines. Cancer Immunol. Res. 10, 1167\u20131174. https:\/\/doi.org\/10.1158\/2326-6066.CIR-22-0362 (2022).","journal-title":"Cancer Immunol. Res."},{"key":"33444_CR41","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12348-022-00321-2","volume":"13","author":"A Martens","year":"2023","unstructured":"Martens, A., Schauwvlieghe, P. P., Madoe, A., Casteels, I. & Aspeslagh, S. Ocular adverse events associated with immune checkpoint inhibitors, a scoping review. J. Ophthalmic Inflammat. Infect. 13, 5. https:\/\/doi.org\/10.1186\/s12348-022-00321-2 (2023).","journal-title":"J. Ophthalmic Inflammat. Infect."},{"key":"33444_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2022.102211","volume":"77","author":"D Merkler","year":"2022","unstructured":"Merkler, D., Vincenti, I., Masson, F. & Liblau, R. S. Tissue-resident CD8 T cells in central nervous system inflammatory diseases: Present at the crime scene and \u2026guilty. Curr. Opin. Immunol. 77, 102211. https:\/\/doi.org\/10.1016\/j.coi.2022.102211 (2022).","journal-title":"Curr. Opin. Immunol."},{"key":"33444_CR43","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/imr.12840","volume":"294","author":"C Bridgewood","year":"2020","unstructured":"Bridgewood, C., Sharif, K., Sherlock, J., Watad, A. & McGonagle, D. Interleukin-23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy. Immunol. Rev. 294, 27\u201347. https:\/\/doi.org\/10.1111\/imr.12840 (2020).","journal-title":"Immunol. Rev."},{"key":"33444_CR44","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/s41385-021-00469-5","volume":"15","author":"S Yamana","year":"2022","unstructured":"Yamana, S. et al. Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity. Mucosal Immunol. 15, 351\u2013361. https:\/\/doi.org\/10.1038\/s41385-021-00469-5 (2022).","journal-title":"Mucosal Immunol."},{"key":"33444_CR45","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1002\/cyto.a.22625","volume":"87","author":"S Van Gassen","year":"2015","unstructured":"Van Gassen, S. et al. FlowSOM: Using self-organizing maps for visualization and interpretation of cytometry data. Cytometry A 87, 636\u2013645. https:\/\/doi.org\/10.1002\/cyto.a.22625 (2015).","journal-title":"Cytometry A"},{"key":"33444_CR46","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.medj.2022.05.002","volume":"3","author":"I Korsunsky","year":"2022","unstructured":"Korsunsky, I. et al. Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases. Med 3, 481-518.e414. https:\/\/doi.org\/10.1016\/j.medj.2022.05.002 (2022).","journal-title":"Med"},{"key":"33444_CR47","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/s41467-023-35948-9","volume":"14","author":"JM Mazet","year":"2023","unstructured":"Mazet, J. M. et al. IFN\u03b3 signaling in cytotoxic T cells restricts anti-tumor responses by inhibiting the maintenance and diversity of intra-tumoral stem-like T cells. Nat. Commun. 14, 321. https:\/\/doi.org\/10.1038\/s41467-023-35948-9 (2023).","journal-title":"Nat. Commun."},{"key":"33444_CR48","doi-asserted-by":"publisher","first-page":"eabl5197","DOI":"10.1126\/science.abl5197","volume":"376","author":"C Dom\u00ednguez Conde","year":"2022","unstructured":"Dom\u00ednguez Conde, C. et al. Cross-tissue immune cell analysis reveals tissue-specific features in humans. Science 376, eabl5197. https:\/\/doi.org\/10.1126\/science.abl5197 (2022).","journal-title":"Science"},{"key":"33444_CR49","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/nmeth.2639","volume":"10","author":"S Picelli","year":"2013","unstructured":"Picelli, S. et al. Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat. Method. 10, 1096\u20131098. https:\/\/doi.org\/10.1038\/nmeth.2639 (2013).","journal-title":"Nat. Method."},{"key":"33444_CR50","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkz114","volume":"47","author":"Y Liao","year":"2019","unstructured":"Liao, Y., Smyth, G. K. & Shi, W. The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads. Nucleic Acids Res. 47, e47\u2013e47. https:\/\/doi.org\/10.1093\/nar\/gkz114 (2019).","journal-title":"Nucleic Acids Res."},{"key":"33444_CR51","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8 (2014).","journal-title":"Genome Biol."},{"key":"33444_CR52","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder, P. & Horvath, S. WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics 9, 559. https:\/\/doi.org\/10.1186\/1471-2105-9-559 (2008).","journal-title":"BMC Bioinformatics"},{"key":"33444_CR53","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.157837","author":"AR Cross","year":"2023","unstructured":"Cross, A. R. et al. Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury. JCI Insight https:\/\/doi.org\/10.1172\/jci.insight.157837 (2023).","journal-title":"JCI Insight"},{"key":"33444_CR54","doi-asserted-by":"publisher","first-page":"2921","DOI":"10.1167\/iovs.12-9662","volume":"53","author":"MJ Mattapallil","year":"2012","unstructured":"Mattapallil, M. J. et al. The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL\/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Invest. Ophthalmol. Vis. Sci. 53, 2921\u20132927. https:\/\/doi.org\/10.1167\/iovs.12-9662 (2012).","journal-title":"Invest. Ophthalmol. Vis. Sci."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33444-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33444-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33444-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T09:01:42Z","timestamp":1775206902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33444-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["33444"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-33444-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,3]]},"assertion":[{"value":"2 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"ADF, AW and LW received salary and research support from Janssen Pharmaceuticals. CDP and ADD served as consultants for and\/or received honoraria from Janssen. JSP was employed by Janssen and holds stock in Johnson & Johnson. The other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11330"}}