{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:50:40Z","timestamp":1793152240556,"version":"4.5.0"},"reference-count":41,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"707","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,8,2]]},"abstract":"<jats:p>\n            Glaucoma is the leading cause of irreversible blindness. Currently, most therapeutic strategies aim to reduce elevated intraocular pressure (EIOP), but this does not always halt disease progression. Evidence suggests a role for T cells in glaucoma pathogenesis, but the underlying mechanisms remain largely unknown. Here, we found that the percentage of circulating CD4\n            <jats:sup>+<\/jats:sup>\n            T cells expressing a gut-homing integrin \u03b27 was increased in patients with glaucoma and was associated with disease stage. In an EIOP-triggered glaucoma mouse model, \u03b27\n            <jats:sup>+<\/jats:sup>\n            CD4\n            <jats:sup>+<\/jats:sup>\n            T cells infiltrated the retina in the progressive phase of glaucoma via eliciting retinal endothelial cell expression of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1). MAdCAM-1 was minimally detected in retinas of healthy mice, and neutralization with an MAdCAM-1 antibody ameliorated retinal ganglion cell (RGC) loss and glial activity in mice with glaucoma. We furthermore found that EIOP-induced \u03b27\n            <jats:sup>+<\/jats:sup>\n            CD4\n            <jats:sup>+<\/jats:sup>\n            T cells homed to the gut during the acute phase of glaucoma, which was essential for progressive RGC damage in diseased mice. Gut-homing \u03b27\n            <jats:sup>+<\/jats:sup>\n            CD4\n            <jats:sup>+<\/jats:sup>\n            T cells underwent transcriptional reprogramming, showing up-regulated pathways enriched in autoimmune diseases, bacteria responses, mucosal immunity, and glial activity. Gut-homing \u03b27\n            <jats:sup>+<\/jats:sup>\n            CD4\n            <jats:sup>+<\/jats:sup>\n            T cells gained the competence to induce retinal MAdCAM-1 expression and to cross the blood-retina barrier. Together, our study reveals a role of gut-licensed \u03b27\n            <jats:sup>+<\/jats:sup>\n            CD4\n            <jats:sup>+<\/jats:sup>\n            T cells and MAdCAM-1 in RGC degeneration and emphasizes the importance of the \u201cgut-retina\u201d axis in glaucoma.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adg1656","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T17:58:55Z","timestamp":1690999135000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":50,"title":["Gut-licensed \u03b27\n            <sup>+<\/sup>\n            CD4\n            <sup>+<\/sup>\n            T cells contribute to progressive retinal ganglion cell damage in glaucoma"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0228-1833","authenticated-orcid":true,"given":"Chong","family":"He","sequence":"first","affiliation":[{"name":"Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, China."},{"name":"Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science and Technology of China, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7645-5262","authenticated-orcid":true,"given":"Wenbo","family":"Xiu","sequence":"additional","affiliation":[{"name":"Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6211-2044","authenticated-orcid":true,"given":"Qinyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9661-1868","authenticated-orcid":true,"given":"Kun","family":"Peng","sequence":"additional","affiliation":[{"name":"Health Management Center, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2570-5655","authenticated-orcid":true,"given":"Xiong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, China."},{"name":"Department of Prenatal Diagnosis, Chengdu Women's and Children\u2019s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4888-8491","authenticated-orcid":true,"given":"Zuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, China."},{"name":"Department of Clinical Laboratory, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8509-641X","authenticated-orcid":true,"given":"Xiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, 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China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8732-268X","authenticated-orcid":true,"given":"Jing","family":"Fu","sequence":"additional","affiliation":[{"name":"Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2839-955X","authenticated-orcid":true,"given":"Qiwei","family":"Dong","sequence":"additional","affiliation":[{"name":"Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, 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China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3628-5699","authenticated-orcid":true,"given":"Zhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science and Technology of China, Chengdu, China."},{"name":"School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9235-0821","authenticated-orcid":true,"given":"Bolin","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1580-2885","authenticated-orcid":true,"given":"Ping","family":"Shuai","sequence":"additional","affiliation":[{"name":"Health Management Center, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6674-014X","authenticated-orcid":true,"given":"Caiping","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5765-358X","authenticated-orcid":true,"given":"Yilian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Sichuan Provincial 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associated lymphoid tissue","volume":"151","author":"Briskin M.","year":"1997","unstructured":"M. Briskin, D. Winsor-Hines, A. Shyjan, N. Cochran, S. Bloom, J. Wilson, L. M. McEvoy, E. C. Butcher, N. Kassam, C. R. Mackay, W. Newman, D. J. Ringler, Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am. J. Pathol. 151, 97\u2013110 (1997).","journal-title":"Am. J. 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Schippers, J. Hubel, F. Heymann, T. Clahsen, S. Eswaran, S. Schleputz, R. Pullen, N. Gassler, K. Tenbrock, F. Tacke, N. Wagner, MAdCAM-1\/\u03b14\u03b27 integrin-mediated lymphocyte\/endothelium interactions exacerbate acute immune-mediated hepatitis in mice. Gastroenterol. Hepatol. 11, 1227\u20131250.e1 (2021).","journal-title":"Gastroenterol. 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