Group 2 innate lymphoid cell (ILC2) signaling pathway (ILC2)

Group 2 innate lymphoid cells (ILC2s) are a subset of the innate immune system that play a pivotal role in orchestrating type 2 inflammation without the need for antigen-specific recognition (Vivier et al., 2018, Cell). They are primarily localized at mucosal surfaces and are activated by epithelium-derived cytokines, or alarmins, such as IL-33, IL-25, and thymic stromal lymphopoietin (TSLP) (Artis & Spits, 2015, Nature). Once activated, ILC2s are potent producers of interleukin-5 (IL-5) and interleukin-13 (IL-13), which drive the recruitment of eosinophils and promote mucus hypersecretion and airway remodeling (Scanlon & McKenzie, 2012, JEM). While these cells are essential for maintaining tissue homeostasis and defending against helminthic infections, their chronic overactivation is strongly linked to the pathogenesis of allergic asthma, atopic dermatitis, and chronic rhinosinusitis (Hammad & Lambrecht, 2021, Nature Reviews Immunology). Therapeutic interventions targeting this pathway include monoclonal antibodies that block the upstream alarmins or the downstream cytokines and their respective receptors (Corren et al., 2017, NEJM). Consequently, the ILC2 signaling axis represents a major focus for precision medicine in treating refractory type 2-high inflammatory diseases.

Other names

Type 2 innate lymphoid cellsNuocytesNatural helper cellsInnate helper 2 cellsIh2 cells

Inhibition of upstream alarmin signaling (TSLP, IL-33, IL-25) or neutralization of downstream effector cytokines (IL-5, IL-13) and their receptors to suppress ILC2-driven type 2 inflammation.