Nat Rev Gastroenterol Hepatol. 2023 Apr 17. doi: 10.1038/s41575-023-00768-1.Online ahead of print.

Bram Verstockt ^1 2, Azucena Salas ³, Bruce E Sands ⁴, Clara Abraham ⁵, Haim Leibovitzh ⁶, Markus F Neurath ^7 8, Niels Vande Casteele ⁹; Alimentiv Translational Research Consortium (ATRC)

Author information

Collaborators

Alimentiv Translational Research Consortium (ATRC): 

Silvio Danese, Geert D'Haens, Lars Eckmann, William A Faubion, Brian G Feagan, Vipul Jairath, Christopher Ma, Saurabh Mehandru, Julian Panes, Florian Rieder, William J Sandborn, Mark S Silverberg, Marisol Veny, Severine Vermeire, Stefania Vetrano

Affiliations

¹University Hospitals Leuven, Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium.

²KU Leuven Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium.

³Inflammatory Bowel Disease Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.

⁴Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

⁵Department of Medicine, Yale University, New Haven, CT, USA.

⁶Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

⁷Department of Medicine 1, University Erlangen-Nürnberg, Erlangen, Germany.

⁸Deutsches Zentrum Immuntherapie DZI, University Erlangen-Nürnberg, Erlangen, Germany.

⁹Department of Medicine, University of California San Diego, La Jolla, CA, USA. nvandecasteele@ucsd.edu.

Abstract

Interleukin-12 (IL-12) and interleukin-23 (IL-23), which belong to the IL-12 family of cytokines, have a key role in intestinal homeostasis and inflammation and are implicated in the pathogenesis of inflammatory bowel disease. Upon their secretion by antigen-presenting cells, they exert both pro-inflammatory and anti-inflammatory receptor-mediated effects. An increased understanding of these biological effects, particularly the pro-inflammatory effects mediated by IL-12 and IL-23, has led to the development of monoclonal antibodies that target a subunit common to IL-12 and IL-23 (p40; targeted by ustekinumab and briakinumab), or the IL-23-specific subunit (p19; targeted by risankizumab, guselkumab, brazikumab and mirikizumab). This Review provides a summary of the biology of the IL-12 family cytokines IL-12 and IL-23, discusses the role of these cytokines in intestinal homeostasis and inflammation, and highlights IL-12- and IL-23-directed drug development for the treatment of Crohn's disease and ulcerative colitis.