The Role of Innate Lymphoid Cells in Autoimmune, Allergic and Infectious Diseases: A Systematic Review.

Abstract

Innate lymphoid cells (ILCs) are tissue-resident immune cells that functionally mirror CD4+ T helper (Th)1, Th2 and Th17 cells, and are accordingly classified as ILC1, ILC2 and ILC3. Additional members of the ILC family include lymphoid tissue inducer (LTi) cells and natural killer (NK) cells. Abundant at barrier surfaces, ILCs are among the first responders to pathogens, contributing to tissue homeostasis and adaptive immunity. This systematic review, conducted following PRISMA guidelines, synthesises human clinical evidence on ILCs in autoimmune, allergic and infectious diseases. Relevant peer-reviewed articles published up to December 2025 were identified across major databases. From 2545 initial records, 170 were selected for full-text evaluation and 135 were ultimately included. Findings were heterogeneous, with the most consistent evidence demonstrating: (i) in inflammatory bowel disease (IBD), a plasticity-driven shift from protective IL-22+ ILC3s to pathogenic IFN-γ+ ILC1s compromises mucosal barrier integrity; (ii) in multiple sclerosis, enrichment of regulatory CD56bright NK cells marks clinical success, while Group 3 ILCs are implicated in meningeal ectopic lymphoid neogenesis; (iii) in systemic lupus erythematosus, expanded IFN-γ+ ILC1s correlate with disease severity and amplify pathogenic Type I interferon responses; and (iv) in allergic diseases (asthma, allergic rhinitis and chronic rhinosinusitis), activated ILC2s drive self-perpetuating inflammatory circuits and tissue remodelling. Future studies should address potential sources of heterogeneity and establish a consensus regarding the role of ILCs in disease pathogenesis to enhance their potential as targets for novel diagnostic and therapeutic strategies.