Innate lymphoid cells in rheumatoid arthritis as mediators of pathology and resolution

Innate lymphoid cells (ILCs) are emerging as critical modulators of inflammation in rheumatoid arthritis, contributing to both disease pathology and resolution. Group 3 ILCs (ILC3s) mirror TH17 cells in their production of IL-17A and IL-22, promoting fibroblast activation, neutrophil recruitment and synovial inflammatory cascades. By contrast, group 2 ILCs (ILC2s) engage reparative and immunoregulatory pathways via secretion of IL-9, IL-13 and IL-10. Lymphoid tissue inducer (LTi) ILCs contribute to ectopic lymphoid tissue neogenesis and stromal remodelling in early disease. Clinically, alterations in ILC subset composition correlate with disease activity, therapeutic responsiveness and inflammatory burden. Advances in high-dimensional immunophenotyping, spatial transcriptomics and single-cell multi-omics now enable precise mapping of ILC subsets and their effector programmes across peripheral blood and synovial tissue, supporting their use in biomarker discovery and treatment pipelines. Furthermore, modulation of ILCs by targeting upstream cytokines, signalling pathways or the use of microbiota-derived metabolites is a potential therapeutic strategy. Finally, cell-based avenues include IL-10-producing ILC2s (ILC210) and engineered chimeric antigen receptor (CAR)-ILC2s for targeted, tissue-resident immune modulation. Although still in the preclinical stages, these approaches highlight the translational potential of ILCs as biomarkers and therapeutic targets in rheumatoid arthritis. Innate lymphoid cells (ILCs) influence rheumatoid arthritis by amplifying inflammatory circuits through ILC3 activity and promoting immune regulation via ILC2 responses. These context-dependent functions position ILC subsets as emerging biomarkers and targets for innovative therapies.