TY - JOUR
T1 - IL-12 and IL-23 pathway inhibition in inflammatory bowel disease
AU - Verstockt, Bram
AU - Salas, Azucena
AU - Sands, Bruce E.
AU - Abraham, Clara
AU - Leibovitzh, Haim
AU - Neurath, Markus F.
AU - Vande Casteele, Niels
AU - Danese, Silvio
AU - D’Haens, Geert
AU - Eckmann, Lars
AU - Faubion, William A.
AU - Feagan, Brian G.
AU - Jairath, Vipul
AU - Ma, Christopher
AU - Mehandru, Saurabh
AU - Panes, Julian
AU - Rieder, Florian
AU - Sandborn, William J.
AU - Silverberg, Mark S.
AU - Veny, Marisol
AU - Vermeire, Severine
AU - Alimentiv Translational Research Consortium (ATRC)
AU - Vetrano, Stefania
N1 - Funding Information:
The authors would like to thank L. M. Shackelton and S. Donegan for critical technical review and editing. B.V. is supported by the Clinical Research Fund (KOOR) at the University Hospitals Leuven and the Research Council at KU Leuven. N.V.C. is supported in part by the NIDDK-funded San Diego Digestive Diseases Research Center (P30 DK120515).
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85153175854
U2 - 10.1038/s41575-023-00768-1
DO - 10.1038/s41575-023-00768-1
M3 - Review article
C2 - 37069321
SN - 1759-5045
VL - 20
SP - 433
EP - 446
JO - Nature Reviews Gastroenterology and Hepatology
JF - Nature Reviews Gastroenterology and Hepatology
IS - 7
ER -