UCSF

Group 2 innate lymphocytes (ILC2s) are developmentally programmed to generate type 2 cytokines, perhaps creating the opportunity for understanding the origins of dysregulated allergic immune responses accompanied by adaptive Th2 responses. We used a fate-mapping approach to more fully investigate the ontogeny of these cells in the mouse during prenatal, neonatal, and adult life. Using several approaches, we define the neonatal window as a period of vigorous de novo ILC2 generation accompanied by ILC2 activation and proliferation in all tissues of the mouse. ILC2s generated during the neonatal period remain the major constituents of adult ILC2s in the lung and visceral adipose tissue. In contrast, neonatal-labeled ILC2s are progressively replaced by adult-derived ILC2s in skin and small intestine with age, suggesting that different tissue microenvironments influence the survival and/or turnover of ILC2s over the course of adult life. Despite increased ILC2 numbers generated in response to helminthic infection, the proportion of fate-mapped cells does not significantly change, suggesting that proliferation of existing cells rather than generation of new cells is the main mechanism by which ILC2 numbers increase under inflammatory conditions. These data uncover 3 distinct phases of ILC2 ontogeny and reveal unsuspected tissue-specific effects driving the maintenance and turnover of these potentially long-lived tissue resident cells.