Modulation of innate immune cells to create transplant tolerance

Graft loss to rejection remains a key impediment to transplant success, which limits the therapeutic potential of this procedure. Though adaptive immune cells are critical in rejection, recent studies have demonstrated the importance of innate immune cells in dictating transplant outcomes (rejection or survival), highlighting the necessity in therapeutically targeting innate immune cells in the induction of tolerance to organ transplants. However, there are many challenges facing the field, as innate immune system consists of diverse cell types, molecular sensors, and soluble mediators that are different from those in the adaptive system. Also, some innate immune cells mediate graft injury, while others promote transplant survival, making therapeutic targeting of innate immune cells a challenging task. In this chapter, key elements in the innate immune system, their responses to organ transplants, as well as the challenges and opportunities in targeting those elements in favor of transplant survival are reviewed.