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Jianping Gao, Reuben Sana, Larry A Wheeler, Virginia L Calder, Stephen C Pflugfelder, Margarita Calonge, Jerry Y Niederkorn, Michael E Stern; Role of CD147 in Experimental Autoimmune Anterior Uveitis (EAAU). Invest. Ophthalmol. Vis. Sci. 2014;55(13):1876.
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CD147, or extracellular matrix metalloproteinase inducer (EMMPRIN) is a newly classified chemokine receptor for cyclophilin A (CypA). It is implicated in several inflammatory diseases and corneal wound healing. Our study is to investigate the role of CD147 in the pathogenesis of experimental autoimmune anterior uveitis (EAAU).
Experiments were designed to determine if 1) CD147 expressions on T cells from blood, lymphoid tissues and/or anterior chamber (AC) of the eye are upregulated in EAAU disease; 2) CD147 expression is correlated with its ligand CypA; and 3) treatment of anti-CD147 antibody (αCD147, 1mg/kg/D) is effective in attenuating intraocular inflammation in EAAU. Lewis rats were immunized with melanin-associated antigen (MAA) to induce EAAU. Clinical examination was carried out using Slit lamp biomicroscopy over EAAU disease progression. Blood, spleen, cervical lymph nodes, aqueous humor (AH), iris and ciliary bodies (ICB) were harvested at the peak of EAAU (Day19). CD147 expression and activation state of CD4+ T cells were accessed using flow cytometry. The level of CD147, CypA and MMPs in AH and ICB were determined by Western blot or Luminex analysis. Additionally, Jurkat T cells were utilized to determine T cell migratory function regulated via interaction of CD147 and CypA.
CD147 expression on CD4+ T cells from blood, spleen or cervical lymph node were correlated with EAAU disease progression, and upregulated at the peak of inflammation compared to normal controls. A subset, but not all CD4+ T cells and macrophages expressed CD147 after migrating into AC of EAAU rats. CypA levels in AH was increased, concomitant with elevations of CD147, as well as MMP2 in EAAU. Treatment with αCD147 attenuated EAAU clinical severity and inhibited inflammatory cell infiltration in the eye (50% decrease, p=0.04). CypA was chemotactic in inducing Jurkat T cell migration (p<0.01), which was completely abolished by αCD147 (p<0.001).
Leukocyte CD147 upregulation contributes to the pathogenesis of EAAU disease. CD147 and CypA interaction may promote leukocyte migration to the anterior chamber in EAAU. Increased MMP2 may elicit proteolytical cleave of EMC and facilitate inflammatory cell infiltration in the eye.
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