The context-dependent role of group 2 innate lymphoid cells in lung diseases

Group 2 innate lymphoid cells (ILC2s), a subset of innate lymphoid cells (ILCs) lacking antigen-specific receptors and functionally mirroring T helper 2 (Th2) cells, are indispensable components of the innate immune system that lack antigen-specific receptors but phenotypically and functionally mirror T helper 2 (Th2) cells, particularly in their expression of the transcription factor GATA3 and the secretion of type 2 cytokines for mediating type 2 immune responses. ILC2s are tissue-resident cells in mucosal tissues, including the lung, where they play crucial roles in maintaining tissue homeostasis and regulating immune responses. ILC2s are poised to respond to environmental signals such as IL-25, IL-33, and TSLP, which activate and expand ILC2s. Their functions are highly context dependent and influenced by interactions with other immune cells. In this review, we summarize recent findings on the roles of ILC2s in lung diseases, highlighting their typical characteristics and their responsiveness to environmental signals in the context of pulmonary pathology. We also discuss potential therapeutic strategies targeting ILC2s, which may offer new avenues for the treatment of inflammatory lung diseases. Understanding the mechanisms by which ILC2s contribute to lung disease progression will provide valuable insights for the development of novel diagnostic (e.g., ILC2 phenotypic markers) and therapeutic approaches (e.g., targeting ILC2 plasticity or alarmin-ILC2 signaling axes).