Type 2 Innate Lymphoid Cells in Allergic Disease

Abstract

Type II innate lymphoid cells (ILC2) are a novel population of lineage-negative cells that produce high levels of Th2 cytokines IL-5 and IL-13. ILC2 are found in human respiratory and gastrointestinal tissue as well as in skin. Studies from mouse models of asthma and atopic dermatitis suggest a role for ILC2 in promoting allergic inflammation. The epithelial cytokines IL-25, IL-33, and TSLP, as well as the lipid mediator leukotriene D4, have been shown to potently activate ILC2 under specific conditions and supporting the notion that many separate pathways in allergic disease may result in stimulation of ILC2. Ongoing investigations are required to better characterize the relative contribution of ILC2 in allergic inflammation as well as mechanisms by which other cell types including conventional T cells regulate ILC2 survival, proliferation, and cytokine production. Importantly, therapeutic strategies to target ILC2 may reduce allergic inflammation in afflicted individuals. This review summarizes the development, surface marker profile, cytokine production, and upstream regulation of ILC2, and focuses on the role of ILC2 in common allergic diseases.

Keywords: Allergy; ILC2; Type 2 innate lymphoid cells.; asthma; atopic dermatitis; nasal polyps.

Fig. (1)

Interactions and functions of airway ILC2. ILC2 respond to epithelial cytokines TSLP, IL-33, and IL-25 and in turn produce Th2 cytokines. Additional ILC2 stimulation may occur from PGD2 and leukotriene D4 produced by mast cells and macrophages, and inhibitory signals from lipoxin A4. TL1A is also produced by dendritic cells and macrophages and can activate ILC2. ILC2 IL-5 production stimulates eosinophil activation and survival, whereas ILC2 IL-13 induces airway hyperresponsiveness, and along with IL-9, promotes mucus production. ILC2 IL-4 may contribute to Th2 cell differentiation and amphiregulin secreted by ILC2 binds to EGFR in the airway epithelium to induce repair responses.