Modulating ILC2 function for treatment of type 2 airway diseases.

Abstract

Type 2 airway diseases including chronic rhinosinusitis, allergic rhinitis, and asthma remain a major health concern. These disorders are largely characterized by an uncontrolled type 2 immune response with elevated cytokines of IL-4, IL-5 and IL-13, eosinophilic inflammation, goblet cell hyperplasia as well as tissue remodeling. In the last few decades, critical potential roles of innate lymphoid cells (ILCs) in type 2 human diseases have emerged. Unlike their lymphocyte counterpart T cells, ILCs lack antigen-specific receptors and are largely tissue resident. Specifically, group 2 innate lymphoid cells (ILC2s) respond to airway epithelium-derived alarmins (TSLP, IL-33) and secrete high levels of type 2 cytokines. ILC2 responses can bypass the activation of T cells as well as develop corticosteroid-resistance. Currently approved biologics targeting the alarmin thymic stromal lymphopoietin (TSLP) or the IL-4/IL-13 receptor may reduce ILC2 activation, though novel treatments of type 2 airway diseases remain needed. In this review, we briefly discuss the pathogenesis of ILC2-mediated airway diseases followed by their current and potential treatments.