Blocking CD200-CD200 receptor axis augments NOS-2 expression and aggravates experimental autoimmune uveoretinitis in Lewis rats

Abstract

Purpose: Tissue expression of CD200 generates inhibitory or down-regulatory signals to macrophages and microglia within CNS and retina. Our interests were to investigate whether blocking CD200 receptor (CD200R) signalling in vivo results in macrophage activation and thus aggravation of EAU in Lewis rats.

Methods: Retinal extract-immunised Lewis rats were treated day 3 and 5 post-immunisation with CD200R mAb or normal mouse serum. Phenotypic analysis of the leucocyte infiltrate and disease severity was clinically and histogically examined.

Results: Rats administered with CD200R mAb developed earlier onset of EAU and more severe disease. Blocking CD200R increased retinal neuronal CD200 expression and, although disease severity was increased concomitant with an increase in NOS-2 expression, retinal macrophage numbers were not increased.

Conclusions: Contemporaneous with data from CD200KO mice, these results support the notion that CD200-CD200R signalling suppresses macrophage activation. Exacerbation of EAU in both CD200KO mice and Lewis rats when CD200-CD200R interaction is blocked suggests that this could be an avenue for therapeutic intervention.