SUN-144 REGULATORY INNATE LYMPHOID CELLS SUPPRESS INNATE IMMUNITY AND REDUCE RENAL ISCHEMIA/REPERFUSION INJURY

Abstract

Innate lymphoid cells (ILCs) are a recently recognized group of immune cells with critical roles in tissue homeostasis and inflammation. Regulatory innate lymphoid cells (ILCregs) are a newly identified subset of ILCs, which play a suppressive role in the innate immune response, favoring the resolution of intestinal inflammation. However, the expression and role of ILCregs in kidney has not been reported. ILCregs were assessed by flow cytometry in human and mouse kideny. Mouse ILCregs isolated from IL-10-GFP mice were used for phenotypic and functional analysis. Bilateral renal ischemia was imposed in C57BL/6 or Rag-/- mice. Adoptive transfer of ILCregs into mice with ischemia/reperfusion injury (IRI) was used to assess their in vivo functions. IL-2C was given by 3 consecutive daily injections prior to IRI operation to inducing expansion of ILCregs in vivo. Here, we show that ILCregs are present in both human and mouse kidney. Human and mouse renal ILCregs expressed similar surface markers and formed a similar proportion of total kidney ILCs. ILCregs from kidney were expanded in vitro with a combination of IL-2, IL-7 and TGF-β. The expanded ILCregs exhibited immunosuppressive effects on innate immune cells, such as ILC1 and macrophages, via secretion of IL-10 and TGF-β. Adoptive transfer of ex vivo expanded ILCregs improved renal function and attenuated histologic damage when administered before or after induction of IRI, in association with reduction of neutrophil infiltration and induction of M2 macrophages in kidney. Moreover, treatment with IL-2/IL-2Ab complexes (IL-2C) promoted expansion of ILCregs in vivo, and prevent renal IRI in Rag-/- mice. Depletion of ILCregs with anti-CD25 Ab abolished the beneficial effects of IL-2C in Rag-/- mice. This study shows that ILCregs protect against renal IRI through suppressing innate renal inflammation. This work demonstrates a novel strategy of manipulating ILCregs to treat kidney disease.