Distinguishing Features of ILC2s During Type 2 Immune Responses

TL;DR

This paper explores the unique roles of ILC2s in type 2 immune responses, highlighting their distinct functions compared to Th2 cells in maintaining tissue balance and fighting infections.

Contribution

The paper identifies nonredundant functions of ILC2s in type 2 immunity, emphasizing their interactions with nonimmune cells.

Findings

ILC2s regulate effector functions and respond rapidly during inflammation.

ILC2s interact with epithelial cells and neurons to orchestrate type 2 immune responses.

Expulsion of gut nematodes requires ILC2-derived cytokines and epithelial cell coordination.

Abstract

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.

Group 2 innate lymphoid cells (ILC2s) are tissue‐resident cells regulated by diverse signals often emanating from surrounding nonhematopoietic cells at barrier surfaces. Their effector cytokines determine tissue homeostasis at steady state and during type 2 immunity in allergies or worm infections. Redundant and unique functions of ILC2s and T cells are assessed in this context.

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