IL-10 producing type 2 innate lymphoid cells prolong islet allograft survival

Type 2 innate lymphoid cells (ILC2s) are a subset ofILCs with critical roles in immunoregulation. However, the possible role ofILC2s as immunotherapy against allograft rejection remains unclear. Here, we show thatIL-33 significantly prolonged islet allograft survival.IL-33-treated mice had elevated numbers ofILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect ofIL-33 on allograft survival, and additionalILC2 depletion in Treg-depletedDEREGmice completely abolished the protective effects ofIL-33, indicating thatILC2s play critical roles inIL-33-mediated islet graft protection. Two subsets ofILC2s were identified in islet allografts ofIL-33-treated mice:IL-10 producingILC2s (ILC2(10)) and non-IL-10 producingILC2s (non-ILC10). Intravenous transfer ofILC2(10)cells, but not non-ILC10, prolonged islet allograft survival in anIL-10-dependent manner. Locally transferredILC2(10)cells led to long-term islet graft survival, suggesting thatILC2(10)cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role ofILC2(10)in islet transplantation which could be potentiated as a therapeutic strategy.