Jack Antel

Microglia are central participants in regulating and effecting immune responses that occur within the central nervous sytem (CNS). Microglia cells are considered to be bone marrow derived cells that are distributed in association with the cerebral microvasculature (perivascular microglia) or within the substance of the CNS (parenchymal microglia). The former are characterized by a relatively high turnover rate and by expression the cell surface regulatory molecules required of competent antigen presenting cells (APCs), consistent with functional data derived from animal models. Parenchymal microglia have a slow turnover rate. These cells also serve to regulate the immune response within the CNS both by serving as APCs and by production of cytokines (IL-12) that direct the production of inflammatory cytokines (Th1 vs Th2) by T cells. Microglia/T cell interactions are bi-directional dependent on signaling via cell-cell interactions (CD40:CD40L; CD80/86:CD28) and soluble molecules (cytokines). Interaction is dependent on the state of activation of the participating cells. In context of autoimmune disease, the network could be activated by systemic T cells infiltrating the CNS. Conversely, the cascade could be initiated by events within the CNS such as infection, tissue injury, or presence of dying cells, to which the microglia can respond as constituents of the innate immune system. Activated microglia can participate in immune effector responses via production of an array of soluble molecules (cytokines, proteases, excitotoxins) or by acting in concert with constituents of the adaptive immune system eg. antibody (antibody dependent cell cytotoxocity). Conversely, microglia may also produce molecules supportive of cell survival and regeneration.(eg neurotrophins). Whether this balance of effector and protective properties can be manipulated for therapeutic purposes remains an ongoing challenge.