{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:26:39Z","timestamp":1790483199699,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2008,2,1]],"date-time":"2008-02-01T00:00:00Z","timestamp":1201824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In rheumatoid arthritis (RA), the synovium is infiltrated by mononuclear cells that influence the proliferation and activation of fibroblast-like synoviocytes (FLS) through soluble mediators as well as cell-to-cell contact. To identify receptor-ligand pairs involved in this cross-talk, we cocultured T cells with FLS lines isolated from synovial tissues from RA patients. Coculture with T cells induced phosphorylation of Akt (Ser473) and its downstream mediators, GSK-3\u03b1\/GSK-\u03b2, FoxO1\/3a, and mouse double minute-2, and enhanced FLS proliferation. T cell-mediated phospho-Akt up-regulation was unique for FLS as no such effect was observed upon interaction of T cells with dendritic cells and B cells. Akt activation was induced by all functional T cell subsets independent of MHC\/Ag recognition and was also found with other leukocyte populations, suggesting the involvement of a common leukocyte cell surface molecule. Akt phosphorylation, enhanced in vitro FLS proliferation, and enhanced FLS IL-6 production was inhibited by blocking Abs to CD11a and ICAM-2 whereas Abs to ICAM-1 had a lesser effect. Selective involvement of the LFA-1\u2013ICAM-2 pathway was confirmed by the finding of increased ezrin phosphorylation at Tyr353 that is known to be downstream of ICAM-2 and supports cell survival through Akt activation. CD28\u2212 T cells, which are overrepresented in RA patients, have high CD11a cell surface expression and induce Akt phosphorylation in FLS more potently than their CD28+ counterparts. These findings identify ICAM-2 as a potential therapeutic target to inhibit FLS activation in RA, allowing for a more selective intervention than broad LFA-1 inhibition.<\/jats:p>","DOI":"10.4049\/jimmunol.180.3.1971","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T22:54:53Z","timestamp":1397861693000},"page":"1971-1978","source":"Crossref","is-referenced-by-count":27,"title":["Synoviocyte Stimulation by the LFA-1\u2013Intercellular Adhesion Molecule-2\u2013Ezrin\u2013Akt Pathway in Rheumatoid Arthritis"],"prefix":"10.1093","volume":"180","author":[{"given":"Karnail","family":"Singh","sequence":"first","affiliation":[{"name":"Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ine\u0301s","family":"Colmegna","sequence":"additional","affiliation":[{"name":"Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"He","sequence":"additional","affiliation":[{"name":"Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia M","family":"Weyand","sequence":"additional","affiliation":[{"name":"Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u0308rg J","family":"Goronzy","sequence":"additional","affiliation":[{"name":"Kathleen B. and Mason I. 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