Innate Lymphoid Cells in Airway Inflammation

Airways are constantly exposed to antigens and various pathogens. Immune cells in the airways act as first line defense system against these pathogens, involving both innate and acquired immunity. There is accumulating evidence that innate lymphoid cells, newly identified lymphoid lineage cells, play a critical role in regulating tissue homeostasis and in the pathogenesis of inflammation. Cytokines produced by other cells activate innate lymphoid cells, which in turn produce large amount of cytokines that result in inflammation. Type 2 innate lymphoid cells (ILC2s) are recognized as key component of T helper type 2 (Th2) inflammation, and are known to be elevated in type 2 (T2) human airway diseases (asthma). Th2 cytokines produced by ILC2s amplify inflammation via activation of eosinophils, B cells, mast cell, and macrophages. "T2 high asthma" has an increased Th2 response triggered by elevation of IL-4, IL-5 and IL-13 and other inflammatory mediators, leading to increased eosinophilic inflammation. The growing evidence of ILC2 contribution in the induction and maintenance of allergic inflammation suggests that targeting upstream mediators may affect both the innate and adaptive immune responses and all disease phenotypes. Blocking ILC2 activators, activation of inhibitory pathways of ILC2, or suppression of ILC2-mediated pathways may be therapeutic strategies for the type 2 airway diseases.