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Lingjun Zhang, Brent A Bell, Chi-Chao Chan, Rachel R Caspi, john Fung, Xiaomin Zhang, Feng Lin; Deficiency of complement anaphylatoxin receptors leads to ameliorated experimental autoimmune uveitis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3204.
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© ARVO (1962-2015); The Authors (2016-present)
Previous reports suggest that complement anaphylatoxin receptors (C3aR/C5aR) could regulate T cell responses through different mechansims, however, the role of these complement receptors in the pathogenesis of experimental autoimmune uveitis (EAU) remains elusive. This study is to clarify the importance of these complement receptors in the development of EAU.
WT and C3aR/C5aR knockout (KO) mice (C57BL/6J background) were immunized with an interphotoreceptor retinoid binding protein (IRBP) peptide to induce EAU following a newly established protocol which induces more severe EAU in B6 mice than the tranditional method. After immunization, the development of EAU was monitored by indirect ophthalmoscopy, and clinical scores were assigned according to previously published criteria. Two weeks after immunization, mice were also examined by scanning laser ophthalmoscopy (SLO) and spectral-domain optical coherence tomography (OCT), followed by histopathological analysis of the eyes and antigen-specific Th1/Th17 recall assays using splenocytes from the mice. In addition, the same number of in vitro activated T cells from immunized WT or KO donors were adoptively transferred to naïve WT recipients and the development of EAU was assessed by regular indirect ophthalmoscopy.
C3aR/C5aR KO mice developed significantly milder EAU than WT controls as judged by clinical scores, retinal histopathology scores, and SLO and OCT analyses. Consistent with the imaging results, C3aR/C5aR KO mice also demonstrated reduced IRBP-specific Th1 and Th17 responses compared with WT mice. In addition, adoptive transfer of activated T cells from immunized C3aR/C5aR KO donors induced less severe EAU in naïve recipients than the same numbers of cells from WT immunized donors.
Complement anaphylatoxin receptors C3aR and C5aR are required for the development of EAU, suggesting that targeting these receptors could be a valid approach for treating patients with autoimmune uveitis.
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