The interplay between innate immune memory and adaptive immunity: Emerging mechanisms in alloimmunity.

Innate immune memory is increasingly recognized as a regulator of immune responses in solid organ transplantation. Following an initial stimulus, innate immune cells and their progenitors can undergo epigenetic and metabolic reprogramming, resulting in enhanced or suppressed proinflammatory responses upon subsequent encounters, termed trained immunity and innate immune tolerance, respectively. These antigen-independent forms of innate immune memory are complemented by donor-specific innate immune memory. Importantly, innate immune memory may influence alloimmune responses by shaping adaptive T cell activation through altered cytokine production, antigen presentation, and costimulatory signals. Conversely, adaptive immune cells can regulate the induction of innate immune memory, highlighting a bidirectional innate-adaptive crosstalk. In this review, we discuss the interplay of innate immune memory with adaptive immunity, and the potential to harness this mechanism to promote graft survival and long-term tolerance.