Innate Lymphoid Cells in Tissue Homeostasis and Diseases

Innate lymphoid cells (ILCs) are tissue-resident immune sentinels that play pivotal roles in maintaining tissue homeostasis, orchestrating immune responses, and modulating metabolic balance. They rapidly respond to environmental cues and interplay with other immune cells, thereby mediating host defense and facilitating tissue repair. However, dysregulation of ILC responses is increasingly implicated in the pathogenesis of a broad spectrum of diseases. This review provides a comprehensive overview of ILC biology, beginning with their classification, plasticity, and homeostatic functions. We then dissect the complex, dual roles of ILCs across various pathological conditions. Using sepsis as a paradigmatic example of immune dysregulation, we illustrate how ILCs orchestrate both protective immunity and pathological role in a context-dependent manner. Furthermore, we extend the discussion to cancer, chronic inflammatory diseases, and metabolic disorders, highlighting the tissue-specific functions of ILC subsets. Finally, we synthesize emerging ILC-targeted therapeutic strategies and future research directions, proposing that a nuanced understanding of ILC biology is essential for developing novel immunotherapies aimed at restoring immune homeostasis in human diseases.