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In an attempt to identify cell surface proteins that play a role in RPE cell\u2013cell interactions, we have considered studying the expression, regulation, and signaling of ADGRE5\/CD97, an adhesion G protein\u2013coupled receptor family member, based on its known adhesive function in other cell types such as leukocytes. We showed that RPE cells express three isoforms of CD97 and identified inflammation\u2010related cytokines as important mediators regulating CD97 expression. Whereas TNF\u2010\u03b1 and IFN\u2010\u03b3 upregulated CD97, TGF\u2010\u03b2 decreased CD97 expression. Due to interaction with CD55, ARPE\u201019 cells firmly adhered to monocytes and T lymphocytes when overexpressing CD97, suggesting a role for CD97 in controlling leukocyte infiltration across the RPE\u2010based blood\u2013retinal barrier. CD97\u2010mediated signaling acted synergistically with PDGF\u2010BB and IFN\u2010\u03b3 to regulate cell growth and survival, ensuring a cellular balance under inflammatory conditions. These findings suggest that CD97 on RPE cells serves to control leukocyte activation and trafficking in uveoretinal inflammation while at the same time regulating second messenger\u2010mediated gene expression, cell growth, and survival.<\/jats:p>","DOI":"10.1111\/nyas.14210","type":"journal-article","created":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T12:45:52Z","timestamp":1565354752000},"page":"64-79","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The role of ADGRE5\/CD97 in human retinal pigment epithelial cell growth and survival"],"prefix":"10.1111","volume":"1456","author":[{"given":"Wolfram","family":"Eichler","sequence":"first","affiliation":[{"name":"Eye Hospital Leipzig University  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lohrenz","sequence":"additional","affiliation":[{"name":"Eye Hospital Leipzig University  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay\u2010Uwe","family":"Simon","sequence":"additional","affiliation":[{"name":"Rudolf Sch\u00f6nheimer Institute of Biochemistry, Molecular Biochemistry Leipzig University  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Krohn","sequence":"additional","affiliation":[{"name":"Clinic for Gastroenterology and Rheumatology, Hepatology Section Leipzig University  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Lange","sequence":"additional","affiliation":[{"name":"Norwegian Center for Movement Disorders Stavanger University Hospital  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"B\u00fcrger","sequence":"additional","affiliation":[{"name":"Eye Hospital Leipzig University  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Liebscher","sequence":"additional","affiliation":[{"name":"Rudolf Sch\u00f6nheimer Institute of Biochemistry, Molecular Biochemistry Leipzig University  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2004"},{"key":"e_1_2_8_3_1","first-page":"52","article-title":"ICAM\u20101\/LFA\u20101 interactions in T\u2010lymphocyte activation and adhesion to cells of the blood\u2013retina barrier in the rat","volume":"83","author":"Mesri M.","year":"1994","journal-title":"Immunology"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.122.7.1013"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65138-3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1998.00560.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2003.10.013"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8021"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9963"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1995.01100040134039"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(00)00017-3"},{"key":"e_1_2_8_12_1","first-page":"1574","article-title":"Expression of pigment epithelium\u2010derived factor in experimental choroidal neovascularization","volume":"43","author":"Renno R.Z.","year":"2002","journal-title":"Invest. 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