Resolution of inflammation and tissue repair. : The immunology of stroke: from mechanisms to transla

Clearing of dead cells and suppression of inflammation are key events in brain repair. Find-me signals (UTP, ATP) attract microglia and macrophages through P2Y2 receptors. Eat-me signals include UDP, which acts on P2Y6 receptors to stimulate microglial phagocytosis¹¹², and phosphatidylserine (PtdSer), which is translocated to the outer leaflet of the plasma membrane of apoptotic cells¹¹². PtdSer-binding proteins involved in the clearance of dead cells include milk fat globule epidermal growth factor 8 protein on microglia¹¹³ and T cell immunoglobulin and mucin domain-containing molecule 4 (TIM4) on macrophages¹¹². Immunoglobulins directed against CNS antigens, which appear after stroke (Table 2), may also promote phagocytosis by engaging Fc receptors on phagocytic cells. Phagocytosis promotes secretion of IL-10 and TGF-β⁵⁶, which, in turn, suppress antigen presentation, promote T_reg formation, inhibit expression of adhesion molecules in endothelial cells and production of proinflammatory cytokines⁶¹. TGF-β and IL-10 are also neuroprotective^{114, 115} and may facilitate brain repair processes. In addition, lipoxins, resolvins and protectins, metabolites of arachidonic acid and omega-3 fatty acids that play an active part in the resolution of inflammation in other organs⁵⁵, could also contribute to suppress post-ischemic inflammation. Growth factors and MMPs produced by endothelial cells, neurons, astrocytes, oligodendrocytes and microglia are key molecules driving tissue reorganization and repair^{63, 116}.