Interleukin-15 in autoimmunity

• Published in: Cytokine (Philadelphia, Pa.) Vol. 136; p. 155258
• Main Authors: Allard-Chamard, Hugues, Mishra, Hemant K., Nandi, Madhuparna, Mayhue, Marian, Menendez, Alfredo, Ilangumaran, Subburaj, Ramanathan, Sheela
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2020
• Subjects: Autoimmunity; IL-15; Immunotherapy; Rheumatoid arthritis; Type 1 diabetes; Autoimmunity; sIL-15Rα:IL-15; T1D; Treg; LSP; mIL-15Rα; IL-15; IBD; SCID; RA; SSP; UTR; Tg; Type 1 diabetes; Rheumatoid arthritis; Immunotherapy; DC
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2020.155258

•IL-15 in implicated in various autoimmune diseases.•IL-15 is a potential immunotherapeutic target in autoimmunity.•Biologics targeting IL-15 or its receptors are in clinical or pre-clinical stages. Interleukin-15 (IL-15) is a member of the IL-2 family of cytokines, which use receptor complexes containing the common gamma (γc) chain for signaling. IL-15 plays important roles in innate and adaptative immune responses and is implicated in the pathogenesis of several immune diseases. The IL-15 receptor consists of 3 subunits namely, the ligand-binding IL-15Rα chain, the β chain (also used by IL-2) and the γc chain. IL-15 uses a unique signaling pathway whereby IL-15 associates with IL-15Rα during biosynthesis, and this complex is ‘trans-presented’ to responder cells that expresses the IL-2/15Rβγc receptor complex. IL-15 is subject to post-transcriptional and post-translational regulation, and evidence also suggests that IL-15 cis-signaling can occur under certain conditions. IL-15 has been implicated in the pathology of various autoimmune diseases such as rheumatoid arthritis, autoimmune diabetes, inflammatory bowel disease, coeliac disease and psoriasis. Studies with pre-clinical models have shown the beneficial effects of targeting IL-15 signaling in autoimmunity. Unlike therapies targeting other cytokines, anti-IL-15 therapies have not yet been successful in humans. We discuss the complexities of IL-15 signaling in autoimmunity and explore potential immunotherapeutic approaches to target the IL-15 signaling pathway.