Inflammatory group 2 innate lymphoid cells

Abstract

Group 2 innate lymphoid cells (ILC2 cells) are able to produce type 2 cytokines and to mediate type 2 immune protection and tissue homeostasis. ILC2 cells have often been considered to be a single set of cells that respond to IL-33 and/or IL-25. Recent evidence now indicates that ILC2 cells can be grouped into two distinct subsets: homeostatic or natural ILC2s (nILC2 cells); and inflammatory ILC2 cells (iILC2 cells). nILC2 cells reside in barrier tissues and primarily respond to IL-33. They play critical roles not only in immune protection but also in tissue repair and beige fat biogenesis. iILC2 cells are not present in peripheral tissues in the steady state but can be elicited at many sites by helminth infection or IL-25 treatment. IL-25-elicited ilLC2 cells act as transient ILC progenitors with multipotency. They can be mobilized by distinct types of infections to develop into nILC2-like or ILC3-like cells, functioning in corresponding immune responses. The demonstration of the existence of iILC2 cells adds to our understanding of the complexity of ILC2 biology and makes necessary an analysis of the relationship between nILC2 cells and iILC2 cells.

Keywords: IL-25; IL-33; ILC plasticity; iILC2; nILC2.

Fig. 1.

Lineage map of ILC2 development. Both nILC2 and iILC2 share the same progenitor (CHILP) with other helper-like ILC lineages, according to the dependence on IL-7 signaling. RORα is critical for the development of both nILC2 and iILC2, suggesting the possible existence of an ILC2 progenitor But it is also possible that iILC2 cells develop directly from CHILP or directly from the ILCP.