Interleukin-15 in autoimmunity. (December 2020)

• Record Type: Journal Article
• Authors: Allard-Chamard, Hugues; Mishra, Hemant K.; Nandi, Madhuparna; Mayhue, Marian; Menendez, Alfredo; Ilangumaran, Subburaj; Ramanathan, Sheela
• Is Part Of: Cytokine. Volume 136(2020)
• Publication Date: 2020-12
• Subjects: IL-15 -- Autoimmunity -- Rheumatoid arthritis -- Type 1 diabetes -- Immunotherapy; DC dendritic cells -- LSP long signal peptide -- RA rheumatoid arthritis -- IBD inflammatory bowel disease -- mIL-15Rα murine -- SCID severe combined immunodeficient -- sIL-15Rα:IL-15 soluble IL-15Rα:IL-15 -- SSP short signal peptide -- T1D type 1 diabetes -- Tg transgenic -- Treg regulatory T cells -- UTR untranslated region; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2020.155258
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: 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. Abstract: 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.