Insights into Group 2 Innate Lymphoid Cells in Human Airway Disease

Abstract

Recent discoveries have led to the identification of a novel group of immune cells, the innate lymphoid cells (ILCs). The members of this group are divided into three subpopulations: ILC1s, ILC2s, and ILC3s. ILC2s produce Th2 cytokines, IL-4, IL-5, and IL-13, upon activation by epithelial cell-derived cytokines, lipid mediators (cysteinyl leukotrienes and prostaglandin D2), and TNF family member TL1A and promote structural and immune cell responses in the airways after antigen exposure. In addition, ILC2 function is also influenced by inducible T cell costimulator (ICOS)/ ICOS-ligand (ICOS-L) interactions via direct contact between immune cells. The most common airway antigens are allergens and viruses which are highly linked to the induction of airway diseases with underlying type 2 inflammation including asthma and allergic rhinitis. Based on recent findings linking ILC2s and airway Th2 responses, there is intensive investigation into the role of ILC2s in human disease with the hope of a better understanding of the pathophysiology and the discovery of novel potential therapeutic targets. This review summarizes the recent advances made in elucidating ILC2 involvement in human Th2 airway disease.

Evidence for the induction of Th2 inflammation by group 2 innate lymphoid cells in response to prostaglandin D2 and cysteinyl leukotrienes in allergic rhinitis

“…5,6 ILC2 populations are found in several tissues, including the respiratory system, nose and skin, and there are strong correlations between the prevalence of ILC2s and the disease severity of asthma, chronic rhinosinusitis with nasal polyp and atopic dermatitis. 7,8 In our previous study, the prevalence of ILC2s was significantly increased in nasal polyps of patients with eosinophilic chronic rhinosinusitis, and it was positively correlated with the number of infiltrating eosinophils in nasal polyps. 8 However, the role of ILC2s in the pathophysiology of AR is not well understood.…”

Are ILC2s Jekyll and Hyde in airway inflammation?

“…ILC2s have been detected in samples from patients with a number of airway diseases and association studies link them to the pathologies observed in the human airways in response to exposure to environmental allergens and viruses. 94 It has been suggested that circulating human ILC2s are functionally immature and not actively primed for effector functions as they demonstrate low or absent expression of key effector molecules as well as receptors to IL-25 and IL-33, which allow ILC2s to respond to inflammatory signals in the lung. 66,67,76 This contrasts with ILC2s in the mouse, which constitutively express the key effector molecules that define ILC2s.…”

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

“…In mice, TSLP is able to induce expression of costimulatory molecules on DCs [44]. In combination with IL-33 and IL-25, TSLP also participates in recruitment and proliferation of ILC2 in the lungs, leading to the release of pro-T H 2 molecules such as IL-4, IL-5, IL-9, IL-13, and amphiregulin [45], which was recently shown to perpetuate allergic inflammation [46]. TSLP can also modulate several functions of MCs [47], including the release of proinflammatory cytokines such as IL-6, TNF-α, and IL-1β, but not cell degranulation [41].…”