[Post-ischemic innate immunity and its application for novel therapeutic strategy targeting brain inflammation]

Stroke or brain ischemia is one of the major causes of death and disability worldwide. Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. In a mouse stroke model, we have reported that IL-23 produced from infiltrating macrophages induces IL-17 producing T cells. IL-17 is mainly produced from gammadeltaT cells and promotes delayed (day 3-4) ischemic brain damage. We also demonstrated that peroxiredoxin (Prx) family proteins released extracellularly from necrotic brain cells induce expression of inflammatory cytokines including IL-23 in macrophages through activation of Toll-like receptor 2(TLR2) and TLR4, thereby promoting neural cell death. We thus propose that regulation of the IL-23-IL-17 axis including gammadeltaT cells, macrophages, and extracellular Prxs could be a potent neuroprotective tool.