科研之友
微信
新浪微博
Facebook
分享链接
摘要
Stroke induces a catastrophic immune response that involves the global activation of peripheral leukocytes, especially T cells. The human leukocyte antigen-DR alpha 1 domain linked to MOG-35-55 peptide (DR alpha 1-MOG-35-55) is a partial major histocompatibility complex (MHC) class II construct which can inhibit neuroantigen-specific T cells and block binding of the cytokine/chemokine macrophage migration inhibitory factor (MIF) to its CD74 receptor on monocytes and macrophages. Here, we evaluated the therapeutic effect of DR alpha 1-MOG-35-55 in a mouse model of permanent distal middle cerebral artery occlusion (dMCAO). DR alpha 1-MOG-35-55 was administered to WT C57BL/6 mice by subcutaneous injection starting 4 h after the onset of ischemia followed by three daily injections. We demonstrated that DR alpha 1-MOG-35-55 post treatment significantly reduced brain infarct volume, improved functional outcomes, and inhibited the accumulation of CD4(+) and CD8(+) T cells and expression of pro-inflammatory cytokines in the ischemic brain 96 h after dMCAO. In addition, DR alpha 1-MOG-35-55 treatment shifted microglia/macrophages in the ischemic brain to a beneficial M2 phenotype without changing their total numbers in the brain or blood. This study demonstrates for the first time the therapeutic efficacy of the DR alpha 1-MOG-35-55 construct in dMCAO across MHC class II barriers in C57BL/6 mice. This MHC-independent effect obviates the need for tissue typing and will thus greatly expedite treatment with DR alpha 1-MOG-35-55 in human stroke subjects. Taken together, our findings suggest that DR alpha 1-MOG-35-55 treatment may reduce ischemic brain injury by regulating post-stroke immune responses in the brain and the periphery.
