IL-23 past, present, and future: a roadmap to advancing IL-23 science and therapy

  • Front Immunol. 2024 Apr 15:15:1331217. doi: 10.3389/fimmu.2024.1331217.
James G Krueger  1 ,  Kilian Eyerich  2  3 ,  Vijay K Kuchroo  4 ,  Christopher T Ritchlin  5 ,  Maria T Abreu  6 ,  M Merle Elloso  7 ,  Anne Fourie  8 ,  Steven Fakharzadeh  9 ,  Jonathan P Sherlock  10  11 ,  Ya-Wen Yang  9 ,  Daniel J Cua  10 ,  Iain B McInnes  12
Affiliations
  • 1. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, United States.
  • 2. Department of Medicine, Division of Dermatology and Venereology, Karolinska Institute, Stockholm, Sweden.
  • 3. Department of Dermatology and Venereology, Medical Center, University of Freiburg, Freiburg, Germany.
  • 4. Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
  • 5. Allergy, Immunology & Rheumatology Division, Center for Musculoskeletal Research, University of Rochester Medical School, Rochester, NY, United States.
  • 6. Division of Gastroenterology, Department of Medicine, University of Miami Leonard Miller School of Medicine, Miami, FL, United States.
  • 7. Janssen Scientific Affairs, LLC, Horsham, PA, United States.
  • 8. Janssen Research & Development, LLC, San Diego, CA, United States.
  • 9. Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, United States.
  • 10. Janssen Research & Development, LLC, Spring House, PA, United States.
  • 11. Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.
  • 12. College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
PMID: 38686385 DOI: 10.3389/fimmu.2024.1331217
Abstract

Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically dominant regulatory cytokine in a cluster of immune-mediated inflammatory diseases (IMIDs), including psoriasis, psoriatic arthritis, and inflammatory bowel disease. We review IL-23 biology, IL-23 signaling in IMIDs, and the effect of IL-23 inhibition in treating these diseases. We propose studies to advance IL-23 biology and unravel differences in response to anti-IL-23 therapy. Experimental evidence generated from these investigations could establish a novel molecular ontology centered around IL-23-driven diseases, improve upon current approaches to treating IMIDs with IL-23 inhibition, and ultimately facilitate optimal identification of patients and, thereby, outcomes.

Keywords
IL-23; cytokine; immune-mediated inflammatory diseases; inflammatory bowel disease; psoriasis; psoriatic arthritis.