Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs

TLDR

Innate lymphoid cells (ILCs) support barrier immunity, tissue homeostasis, and immune regulation across the body, yet their mechanisms of maintaining presence in lymphoid and peripheral tissues are poorly understood. In adult mice, ILCs are tissue‑resident cells that self‑renew and expand locally under physiological conditions, during systemic immune perturbation, and acute helminth infection, with hematogenous cells partially replenishing the pool at later infection stages.

Abstract

Innate lymphoid cells (ILCs) contribute to barrier immunity, tissue homeostasis, and immune regulation at various anatomical sites throughout the body. How ILCs maintain their presence in lymphoid and peripheral tissues thus far has been unclear. We found that in the lymphoid and nonlymphoid organs of adult mice, ILCs are tissue-resident cells that were maintained and expanded locally under physiologic conditions, upon systemic perturbation of immune homeostasis and during acute helminth infection. However, at later time points after infection, cells from hematogenous sources helped to partially replenish the pool of resident ILCs. Thus, ILCs are maintained by self-renewal in broadly different microenvironments and physiological settings. Such an extreme "sedentary" lifestyle is consistent with the proposed roles of ILCs as sentinels and local keepers of tissue function.