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Lina Zhang, Juan Ma, Masaru Takeuchi, Yoshihiko Usui, Takaaki Hattori, Yoko Okunuki, Naoyuki Yamakawa, Takeshi Kezuka, Masahiko Kuroda, Hiroshi Goto; Suppression of Experimental Autoimmune Uveoretinitis by Inducing Differentiation of Regulatory T Cells via Activation of Aryl Hydrocarbon Receptor. Invest. Ophthalmol. Vis. Sci. 2010;51(4):2109-2117. doi: 10.1167/iovs.09-3993.
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© 2017 Association for Research in Vision and Ophthalmology.
Aryl hydrocarbon receptor (AHR) has been identified as a regulator of CD25+CD4+ regulatory T-cell (Treg) and Th17 cell differentiation in mice, and activation of AHR by its ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces functional Treg cells. In this study, the authors examined whether the AHR-mediated effect of TCDD suppresses mouse experimental autoimmune uveitis (EAU) by inducing Treg cell differentiation.
C57BL/6 mice were injected with TCDD 1 day before immunization with human interphotoreceptor retinoid-binding protein peptide 1–20 (hIRBP-p), and the severity of EAU was assessed clinically and histopathologically. Immunologic responses of draining lymph node cells and splenocytes to hIRBP-p and anti–CD3 monoclonal antibody (mAb) were assessed by T-cell proliferation and cytokine production. In addition, differentiation of Foxp3+ T cells and their immunosuppressive roles in TCDD-injected mice were evaluated.
TCDD injection increased Foxp3+ T cells in the lymph nodes and in the spleen. Development of EAU was completely suppressed by TCDD injection, and suppression was abolished by treatment with anti–CD25 mAb before TCDD injection. Both lymphocytes and splenocytes obtained from TCDD-injected mice immunized with hIRBP-p failed to produce IFN-γ and IL-17 on stimulation with hIRBP-p, and the failure of IL-17 production was observed even when stimulated with anti–CD3 mAb. However, this protocol did not interfere with IL-10 production and T-cell proliferation response when assessed on stimulation with anti–CD3 mAb.
Activation of AHR by TCDD markedly suppressed autoimmune uveoretinitis through mechanisms that expand CD25+Foxp3+ Treg cells and interfere with the activation of Th1 and Th17 cells.
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