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Interleukin-15 in autoimmunity.

Hugues Allard-Chamard1, Hemant K Mishra2, Madhuparna Nandi3

  • 1Division of Rheumatology, Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; Centre de Recherche Clinique, Centre Hospitalier d'Université de Sherbrooke, Sherbrooke, QC, Canada.

Cytokine
|September 12, 2020
PubMed
Summary

Interleukin-15 (IL-15) is crucial for immune responses and autoimmune diseases. Targeting IL-15 shows promise in preclinical models, but human therapies face challenges, necessitating further research into its complex signaling pathways.

Keywords:
AutoimmunityIL-15ImmunotherapyRheumatoid arthritisType 1 diabetes

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Area of Science:

  • Immunology
  • Molecular Biology
  • Autoimmunity

Background:

  • Interleukin-15 (IL-15) is a cytokine in the IL-2 family, utilizing the common gamma (γc) chain for signaling.
  • IL-15 is vital for both innate and adaptive immunity and is linked to the development of numerous immune-related diseases.
  • The IL-15 receptor complex comprises IL-15Rα, IL-2/15Rβ, and γc chains, with IL-15 utilizing a unique 'trans-presentation' signaling mechanism.

Purpose of the Study:

  • To review the complex signaling pathways of IL-15 in the context of autoimmune diseases.
  • To explore the potential of targeting IL-15 signaling for immunotherapeutic strategies in autoimmunity.
  • To discuss the challenges and future directions for anti-IL-15 therapies in humans.

Main Methods:

  • Literature review of IL-15 signaling mechanisms.
  • Analysis of IL-15's role in the pathogenesis of various autoimmune conditions.
  • Examination of preclinical and clinical data regarding IL-15 targeted therapies.

Main Results:

  • IL-15 plays a significant role in the pathology of autoimmune diseases including rheumatoid arthritis, autoimmune diabetes, inflammatory bowel disease, celiac disease, and psoriasis.
  • Preclinical studies demonstrate that inhibiting IL-15 signaling can be beneficial in autoimmune models.
  • Current anti-IL-15 therapies have not yet achieved success in human clinical trials, unlike therapies targeting other cytokines.

Conclusions:

  • IL-15 signaling is complex and implicated in diverse autoimmune diseases.
  • Targeting IL-15 presents a potential therapeutic avenue for autoimmunity, supported by preclinical evidence.
  • Overcoming the challenges in human anti-IL-15 therapies requires a deeper understanding of IL-15's intricate biological functions and signaling.