ILC2 Diversity, Location, and Function in Pulmonary Disease

Type-2 inflammation is driven by the production of canonical type-2 cytokines IL-4, IL-5, and IL-13. Type-2 cytokines promote mucus production, innate immune cell recruitment, and smooth muscle contractility in mucosal tissues. These hallmarks of type-2 inflammation are important contributors to the weep-and-sweep responses observed in the lung and intestine after epithelial insults. While these type-2 cytokines are generated by a number of innate and adaptive immune cells, group 2 innate lymphoid cells (ILC2) are key early producers of these cytokines and are critical in shaping immune responses in the lung. This review summarizes the role of ILC2 in the lung with specific emphasis on their origins as part of the gut-lung axis, their heterogeneity with respect to unique identities of circulating and tissue resident ILC2 populations, and how these relatively rare immune cells can significantly impact the course of pulmonary disease. We also explore factors that influence ILC2 behavior with respect to activation, migration, and communication with their environment.