Distinguishing Features of ILC2s During Type 2 Immune Responses

Innate lymphoid cells (ILCs) are innate immune cells populating many tissues early in ontogeny. ILCs and T cells share basic transcriptional programs, immune modules, and effector functions. This article focuses on ILC2s, a subset capable of producing an array of type 2 cytokines similar to T helper 2 (Th2) cells. While there is a striking overlap in effector functions between ILC2s and Th2 cells, we discuss the distinguishing features and nonredundant functions of ILC2s in homeostasis and during inflammation. These include the regulation of their effector functions, the kinetics of their response, and their spatial distribution. ILC2s interact with different cell types and maintain crosstalk with nonimmune cells, such as epithelial cells, stromal cells, and neurons. We review how neurons and epithelial cells trigger ILC2 responses and depend on ILC2-derived cytokines, leading to the concept that expulsion of many gut-dwelling nematodes is initiated and executed by the intestinal epithelium but strictly requires the type 2 immune response orchestrated by ILC2s.