Interleukin-15 in autoimmunity

Hugues Allard-Chamard, Hemant K. Mishra, Madhuparna Nandi, Marian Mayhue, Alfredo Menendez, Subburaj Ilangumaran, Sheela Ramanathan

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Article number155258
JournalCytokine
Volume136
DOIs
StatePublished - Dec 2020

Bibliographical note

Funding Information:
This work was supported by Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant of SR. MN is the recipient of FRQS post-doctoral fellowship.

Keywords

  • Autoimmunity
  • IL-15
  • Immunotherapy
  • Rheumatoid arthritis
  • Type 1 diabetes

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