{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:55:47Z","timestamp":1778626547381,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T00:00:00Z","timestamp":1658620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the National Eye Institute (NEI) and National Institutes of Health (NIH)","award":["EY000350-15"],"award-info":[{"award-number":["EY000350-15"]}]},{"name":"Intramural Research Program of the National Eye Institute (NEI) and National Institutes of Health (NIH)","award":["EY000280-23"],"award-info":[{"award-number":["EY000280-23"]}]},{"name":"Intramural Research Program of the National Eye Institute (NEI) and National Institutes of Health (NIH)","award":["# 8326997"],"award-info":[{"award-number":["# 8326997"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interleukin-27 is constitutively secreted by microglia in the retina or brain, and upregulation of IL-27 during neuroinflammation suppresses encephalomyelitis and autoimmune uveitis. However, while IL-35 is structurally and functionally similar to IL-27, the intrinsic roles of IL-35 in CNS tissues are unknown. Thus, we generated IL-35\/YFP-knock-in reporter mice (p35-KI) and demonstrated that photoreceptor neurons constitutively secrete IL-35, which might protect the retina from persistent low-grade inflammation that can impair photoreceptor functions. Furthermore, the p35-KI mouse, which is hemizygous at the il12a locus, develops more severe uveitis because of reduced IL-35 expression. Interestingly, onset and exacerbation of uveitis in p35-KI mice caused by extravasation of proinflammatory Th1\/Th17 lymphocytes into the retina were preceded by a dramatic decrease of IL-35, attributable to massive death of photoreceptor cells. Thus, while inflammation-induced death of photoreceptors and loss of protective effects of IL-35 exacerbated uveitis, our data also suggest that constitutive production of IL-35 in the retina might have housekeeping functions that promote sterilization immunity in the neuroretina and maintain ocular immune privilege.<\/jats:p>","DOI":"10.3390\/ijms23158156","type":"journal-article","created":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T22:49:02Z","timestamp":1658702942000},"page":"8156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Photoreceptor Cells Constitutively Express IL-35 and Promote Ocular Immune Privilege"],"prefix":"10.3390","volume":"23","author":[{"given":"Cheng-Rong","family":"Yu","sequence":"first","affiliation":[{"name":"Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-6148","authenticated-orcid":false,"given":"Manoj Kumar","family":"Yadav","sequence":"additional","affiliation":[{"name":"Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minkyung","family":"Kang","sequence":"additional","affiliation":[{"name":"Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingyos","family":"Jittayasothorn","sequence":"additional","affiliation":[{"name":"Immunoregulation Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijin","family":"Dong","sequence":"additional","affiliation":[{"name":"Genetic Engineering Core, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles E.","family":"Egwuagu","sequence":"additional","affiliation":[{"name":"Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/ni.2366","article-title":"IL-12 family cytokines: Immunological playmakers","volume":"13","author":"Vignali","year":"2012","journal-title":"Nat. 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