The Dual Regulatory Roles of Macrophages in Acute Allogeneic Organ Graft Rejection

Innate immune cells are critical for transplant response.As an important cellular component of innate immune cells,macrophages are the predominate infiltrated cells in allografts,and macrophage accumulation in allografts is negatively associated with the short-and long-term outcomes of organ transplantation.Macrophages are functionally heterogeneous and plastic.They participate in organ graft rejection through multiple pathways,including antigen presentation,the expression of costimulatory molecules and cytokines,and direct cytotoxicity and injury ability to allografts.However,some macrophage subpopulations,such as regulatory macrophages,can protect allografts from immune rejection and promote transplant immune tolerance with their immune regulatory properties.Although researchers recognize the potential roles macrophages play in allograft injury,they pay insufficient attention to the diverse roles of macrophages in allograft rejection.We herein briefly summarize the distinctive roles of macrophages in acute transplant immune response and the effect of immunosuppressive drugs on macrophages.Greater attention should be paid to the complex and critical function of macrophages in allograft rejection,and more effort should be put into developing immunosuppressive drugs that specifically target macrophages,which would ultimately improve the long-term survival of organ grafts in patients.

Resolution of inflammation and repair after ischemic brain injury

After ischemic stroke, proinflammatory molecules known as danger-associated molecular patterns (DAMPs) originating from damaged brain cells recruit and activate immune cells (neutrophils, macrophages, lymphocytes) further eliciting innate and adaptive immunity. During the acute phase from day 1 to day 3 of the stroke onset, macrophages play a major role in the progression of inflammation, promoting the destruction of brain tissue. During the recovery phase, from day 3~4 to day 7 after stroke onset, infiltrating macrophages switch to repairing macrophages, which clear the DAMPs and promote tissue repair by producing neurotrophic factors. Adaptive immunity during the late or chronic phase (> day 7) of stroke has not been well investigated. Recent studies have also indicated that antigen-specific T cells, especially regulatory T cells (Tregs), play major roles in neural repair. This review focuses mainly on the resolution of inflammation and tissue repair by macrophages and Tregs.