Cortical CD200–CD200R and CD47–SIRPα expression is associated with multiple sclerosis pathology

Abstract

Abstract Control of microglia activity through CD200–CD200R and CD47–SIRPα interactions has been implicated in brain homeostasis. Here, we assessed CD200, CD47, CD200R and SIRPα expression with qPCR and immunohistochemistry in multiple sclerosis (MS) normal-appearing cortical grey matter (NAGM), normal-appearing white matter (NAWM), cortical grey matter (GM) lesions and perilesional GM, and compared this to control GM and white matter (WM), to investigate possible altered control of microglia in MS. In MS NAGM, CD200 expression is lower compared with control GM, specifically in cortical layers 1 and 2, and CD200 expression in NAGM negatively correlates with the cortical lesion rate. Interestingly, NAGM and NAWM CD200 expression is positively correlated, and NAGM CD200 expression negatively correlates with the proportion of active and mixed WM lesions. In GM lesions, CD200 and CD47 expressions are lower compared with NAGM and perilesional GM. CD200R expression is lower in MS NAGM, whereas SIRPα was increased in and around GM lesions. Taken together, our data indicate that CD200 and CD47 play a role in GM MS lesion formation and progression, respectively, and that targeting CD200 pathways may offer therapeutic avenues to mitigate MS pathology in both WM and GM.