Innate lymphoid cells as central regulators of tissue homeostasis: implications for allergic diseases

Barrier tissues continuously encounter environmental challenges while maintaining immune tolerance and tissue integrity. Preservation of homeostasis within the skin, respiratory tract, and gastrointestinal mucosa requires coordinated communication among epithelial, stromal, neuronal, vascular, and immune cells. Innate lymphoid cells (ILCs) have emerged as key regulators of these processes owing to their strategic localization within barrier tissues and their capacity to rapidly integrate tissue-derived signals. Although initially classified as innate counterparts of helper T-cell subsets, accumulating evidence demonstrates that mature ILC identity is continuously shaped by developmental programming, tissue-specific environmental cues, and functional plasticity. Beyond their established roles in host defense, ILCs regulate epithelial maintenance, tissue repair, extracellular matrix remodeling, neuroimmune communication, and resolution of inflammation through extensive interactions with structural and immune cells. Under physiological conditions, these activities preserve barrier integrity and restore tissue homeostasis following injury. However, persistent epithelial damage and chronic exposure to environmental stimuli disrupt these regulatory networks, resulting in sustained ILC activation, impaired resolution, pathological remodeling, and progressive organ dysfunction. With particular emphasis on ILC2s in allergic disease, this review summarizes recent advances in ILC development, tissue adaptation, and multicellular communication, and examines how disruption of these homeostatic programs contributes to asthma, chronic rhinosinusitis with nasal polyps, eosinophilic gastrointestinal diseases, and atopic dermatitis. Finally, we highlight emerging technologies and future directions that may facilitate restoration of tissue homeostasis as a therapeutic strategy for chronic allergic diseases.