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

Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL‐33 significantly prolonged islet allograft survival. IL‐33‐treated mice had elevated numbers of ILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect of IL‐33 on allograft survival, and additional ILC2 depletion in Treg‐depleted DEREG mice completely abolished the protective effects of IL‐33, indicating that ILC2s play critical roles in IL‐33‐mediated islet graft protection. Two subsets of ILC2s were identified in islet allografts of IL‐33‐treated mice: IL‐10 producing ILC2s (ILC210) and non‐IL‐10 producing ILC2s (non‐ILC 10). Intravenous transfer of ILC210 cells, but not non‐ILC 10, prolonged islet allograft survival in an IL‐10‐dependent manner. Locally transferred ILC210 cells led to long‐term islet graft survival, suggesting that ILC210 cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role of ILC210 in islet transplantation which could be potentiated as a therapeutic strategy.
This study reveals a major protective role of the IL‐33/ILC2 axis in islet transplantation that could be potentiated as a therapeutic strategy. Adoptive transfer of ex vivo expanded IL‐10‐producing ILC2s (ILC210) significantly prolonged allograft survival.