Adoptive transfer of cytokine‐induced immunomodulatory adult microglia attenuates experimental autoimmune encephalomyelitis in DBA/1 mice

摘要: Microglia are resident antigen-presenting cells in the central nervous system (CNS) that either suppress or promote disease depending on their activation phenotype and microenvironment. Multiple sclerosis (MS) is a chronic inflammatory causing demyelination nerve loss CNS, experimental autoimmune encephalomyelitis (EAE) an animal model of MS widely used to investigate pathogenic mechanisms therapeutic effects. We isolated cultured microglia from adult mouse brains exposed them specific combinations stimulatory molecules cytokines, combination IL-4, IL-10, TGF-β yielding optimal regime for induction immunosuppressive (M2). M2 were characterized by decreased expression production CD86, PD-L1, nitric oxide, IL-6, increased PD-L2, having potent capacity retain secondary proinflammatory stimulation. induced regulatory T cells, suppressed T-cell proliferation, downmodulated M1-associated receptor M1 macrophages. Myelin oligodendrocyte glycoprotein (MOG)-induced EAE was DBA/1 mice at different time points (0, 5, 12, 15 days postimmunization) 3 × 105 transferred intranasally. A single transfer attenuated severity established EAE, which particularly obvious when injected postimmunization. microglia-treated had reduced responses less CNS. Our findings demonstrate therapy represents novel intervention alleviated this principle may have relevance treatment patients. GLIA 2014;62:804–817