Innate lymphoid cells (ILC) 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 is currently unknown. We found that in the lymphoid and non-lymphoid organs of adult mice, ILC 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 post-infection, cells from hematogenous sources helped to partially replenish the pool of resident ILCs. Thus, ILC 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.

Mutually exclusive expression of T-bet and Eomes drives the development of distinct NK cell lineages with complementary functions.