{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:50:57Z","timestamp":1790139057622,"version":"4.0.1"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/TA\/010\/2012"],"award-info":[{"award-number":["NMRC\/TA\/010\/2012"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H07303"],"award-info":[{"award-number":["17H07303"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K09467"],"award-info":[{"award-number":["18K09467"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20jk0210029"],"award-info":[{"award-number":["JP20jk0210029"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cytomegalovirus (CMV) causes clinical issues primarily in immune-suppressed conditions. CMV-associated anterior uveitis (CMV-AU) is a notable new disease entity manifesting recurrent ocular inflammation in immunocompetent individuals. As patient demographics indicated contributions from genetic background and immunosenescence as possible underlying pathological mechanisms, we analyzed the immunogenetics of the cohort in conjunction with cell phenotypes to identify molecular signatures of CMV-AU. Among the immune cell types, natural killer (NK) cells are main responders against CMV. Therefore, we first characterized variants of polymorphic genes that encode differences in CMV-related human NK cell responses (Killer cell Immunoglobulin-like Receptors (KIR) and HLA class I) in 122 CMV-AU patients. The cases were then stratified according to their genetic features and NK cells were analyzed for human CMV-related markers (CD57, KLRG1, NKG2C) by flow cytometry. KIR3DL1 and HLA class I combinations encoding strong receptor\u2013ligand interactions were present at substantially higher frequencies in CMV-AU. In these cases, NK cell profiling revealed expansion of the subset co-expressing CD57 and KLRG1, and together with KIR3DL1 and the CMV-recognizing NKG2C receptor. The findings imply that a mechanism of CMV-AU pathogenesis likely involves CMV-responding NK cells co-expressing CD57\/KLRG1\/NKG2C that develop on a genetic background of KIR3DL1\/HLA-B allotypes encoding strong receptor\u2013ligand interactions.<\/jats:p>","DOI":"10.3390\/ijms22073623","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T05:57:18Z","timestamp":1617170238000},"page":"3623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Molecular Signatures of Natural Killer Cells in CMV-Associated Anterior Uveitis, A New Type of CMV-Induced Disease in Immunocompetent Individuals"],"prefix":"10.3390","volume":"22","author":[{"given":"Nobuyo","family":"Yawata","sequence":"first","affiliation":[{"name":"Department of Ocular Pathology and Imaging Science, Kyushu University, Fukuoka 812-8582, Japan"},{"name":"Singapore Eye Research Institute, Singapore 168751, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Shirane","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaing","family":"Woon","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Lim","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6169-290X","authenticated-orcid":false,"given":"Hidenori","family":"Tanaka","sequence":"additional","affiliation":[{"name":"HLA Foundation Laboratory, Kyoto 600-8813, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoh-Ichi","family":"Kawano","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Fukuoka Dental College, Fukuoka 814-0193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Yawata","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research, A*STAR, Singapore 117609, Singapore"},{"name":"Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"},{"name":"National University Health System, Singapore 119228, Singapore"},{"name":"Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore"},{"name":"NUSMED Immunology Translational Research Programme, National University of Singapore, Singapore 117456, Singapore"},{"name":"International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon-Phaik","family":"Chee","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore 168751, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"},{"name":"Ocular Inflammation and Immunology Department, Singapore National Eye Centre, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Siak","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore 168751, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"},{"name":"Ocular Inflammation and Immunology Department, Singapore National Eye Centre, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koh-Hei","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.4049\/jimmunol.1800171","article-title":"Cytomegalovirus: Shape-Shifting the Immune System","volume":"200","author":"Picarda","year":"2018","journal-title":"J. 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