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H. Nakagawa, Y. Usui, Y. Okunuki, T. Kezuka, M. Takeuchi, M. Kuroda, H. Goto; Mesenchymal Stromal Cells (mscs) Suppress Experimental Autoimmune Uveitis (eau) In Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5233.
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Experimental autoimmune uveitis (EAU) has been used as a model for human uveitis in relation to the autoimmune mechanism and proved to be a T-cell mediated autoimmune disease. In recent years, it has been indicated that mesenchymal stromal cells (MSCs) inhibit activation of pathogenic T cells involved in various autoimmune disease models. In this study, we have investigated the effect of ex vivo culture-expanded MSCs on EAU in mice.
EAU was induced by immunization with residues 1-20 of IRBP in CFA with M. tuberculosis H37RA and pertussis toxin in C57BL/6 mice. MSCs (2 x 106 cells/mouse) or vehicle were intravenously transferred into mice on day 0, 1, and 2 post immunization. Eyes were evaluated by clinical evaluation at day 10, 14, and 17 after immunization, and by histopathological criteria at day 21. Immunologic responses were assessed by antigen-specific T-cell proliferation and cytokine production (IFN-γ and IL-10) in vitro.
Mice receiving MSCs significantly inhibited the development of EAU compared with control EAU mice receiving vehicle. Antigen-specific T-cell proliferative response and IFN-γproduction were significantly reduced but IL-10 production was increased in cervical and submandibular lymph node cells from MSCs-treated mice compared to controls.
Our study demonstrates that MSCs selectively downregulate antigen-specific responses through at least suppression of Th1 cell expansion, by which the development of EAU was inhibited. In vitro manipulation of MSCs could be a potential therapy for human uveitis in particular and autoimmune diseases in general.
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