title: Interleukin-23: a key cytokine in inflammatory diseases.
abstract: Interleukin-23 (IL-23) is a pro-inflammatory cytokine composed of two subunits, p19 and p40. The p40 subunit is shared with IL-12. IL-23 and IL-12 have different receptors and different effects. Whereas IL-12 induces development of Th1 cells, which produce interferon-γ, IL-23 is involved in differentiation of Th17 cells in a pro-inflammatory context and especially in the presence of TGF-β and IL-6. Activated Th17 cells produce IL-17A, IL-17F, IL-6, IL-22, TNF-α, and GM-CSF. Inflammatory macrophages express IL-23R and are activated by IL-23 to produce IL-1, TNF-α, and IL-23 itself. These effects identify IL-23 as a central cytokine in autoimmunity and a highly promising treatment target for inflammatory diseases. IL-23 is found in the skin of patients with psoriasis, in the bowel wall of patients with chronic inflammatory bowel disease, and in synovial membrane of patients with rheumatoid arthritis. IL-23 is involved in osteoclastogenesis, independently from IL-17, via induction of RANKL expression. Debate continues to surround the role for IL-23 in the pathophysiology of inflammatory joint diseases (rheumatoid arthritis and spondyloarthritis). Ustekinumab, which inhibits IL-12 and IL-23 by blocking p40, has been found effective in cutaneous psoriasis and psoriatic arthritis, as well as in Crohn's disease. Treatments that specifically target IL-23 (antibodies to p19) are being developed.
authors.affiliation: Sorbonne Paris Cité Université Paris, Bobigny France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Duvallet
authors.forename: Luca
authors.initials: L
authors.lastname: Semerano
authors.forename: Eric
authors.initials: E
authors.lastname: Assier
authors.forename: Géraldine
authors.initials: G
authors.lastname: Falgarone
authors.forename: Marie-Christophe
authors.initials: MC
authors.lastname: Boissier
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism*; D053760:Interleukin-23 Subunit p19 / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism
chemical_list: D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D018664:Interleukin-12