Recent evidence supports a model in which the pool of adult immune cells is actually composed of cells derived from fetal, neonatal, and adult waves of hematopoiesis. In this review, we discuss this evidence in the context of innate lymphoid cells (ILC), with a focus on the environmental signals required for their development during early life.

ABSTRACT

Our expanding knowledge of innate lymphoid cells (ILCs) over the last two decades has demonstrated the pivotal role these cells play in homeostasis and host defense. Recent work suggests that the observed heterogeneity within different ILC types can be linked to their ontogeny in early life, indicating that the fetal environment likely influences ILC development and function. In this review, we aim to summarize the current understanding of how cell-extrinsic factors shape ILC emergence in early life. By examining the combined effects of progenitor cell origin and the signals they receive, we highlight the major environmental cues important for establishing ILC potential. Furthermore, we summarize the key factors for the production of each of the three groups of ILCs, while identifying outstanding questions regarding when and how these signals influence ILC development. Altogether, this review describes our evolving understanding of the interplay between ILC ontogenic origin and environmental signals in early life, and establishes key areas for further work to clarify how specific signals drive ILC development.