Implications for Interleukin-33 in solid organ transplantation

Interleukin(IL)-33 is a member of the IL-1 cytokine family that has been attributed T helper (Th) type 2 immunity-promoting capacity. However, new studies indicate that IL-33 is a multifunctional protein that acts as transcriptional/signaling repressor, functions as an alarmin alerting the immune system to necrosis, as well as serves as a cytokine that targets cells expressing ST2, the IL-33 receptor. Interestingly, IL-33 is also emerging as a pleiotropic cytokine. Depending on the innate or adaptive immune cells targeted by IL-33, it can not only promote type 2, but also IFN-γ dominated type 1 immunity. In addition, IL-33 expands regulatory T cells. In this review, we assimilate the current knowledge of IL-33 immunobiology and discuss how IL-33 may mediate such diverse roles in the immune response to pathogens and development of immune-mediated pathologies. The function of IL-33 in shaping alloimmune responses to transplanted organs is poorly explored, but a particularly beneficial role of IL-33 in experimental heart transplant models is summarized. Finally, given the implication of IL-33 in pathologies of the lung and intestine, we discuss how IL-33 may contribute to the comparatively poor outcomes following transplantation of these two organs.