Unravelling the immunobiology of innate lymphoid cells (ILCs): Implications in health and disease

Abstract

Innate lymphoid cells (ILCs), a growing class of immune cells, imitate the appearance and abilities of T cells. However, unlike T cells, ILCs lack acquired antigen receptors, and they also do not undergo clonal selection or proliferation in response to antigenic stimuli. Despite lacking antigen-specific receptors, ILCs respond quickly to signals from infected or damaged tissues and generate an array of cytokines that regulate the development of adaptive immune response. ILCs can be categorized into four types based on their signature cytokines and transcription factors: ILC1, ILC2, ILC3 (including Lymphoid Tissue inducer- LTi cells), and regulatory ILCs (ILCregs). ILCs play key functions in controlling and resolving inflammation, and variations in their proportion are linked to various pathological diseases including cancer, gastrointestinal, pulmonary, and skin diseases. We highlight current advancements in the biology and classification of ILCs in this review. Additionally, we provide a thorough overview of their contributions to several inflammatory bone-related pathologies, including osteoporosis, rheumatoid arthritis, periodontitis, and ankylosing spondylitis. Understanding the multiple functions of ILCs in both physiological and pathological conditions will further mobilize future research towards targeting ILCs for therapeutic purposes.

Keywords: Ankylosing spondylitis; Asthma; Bone; COPD; COVID-19; Cancer; Diabetes; Inflammatory bowel disease (IBD); Innate lymphoid cells (ILCs); Obesity; Osteoporosis; Periodontitis; RA.