title: IL-23 and IL-27: new members of the growing family of IL-12-related cytokines with important implications for therapeutics.
abstract: The recent discoveries of the two interleukin (IL)-12-related cytokines, IL-23 and IL-27, reveal that the regulation of cellular immunity is more complex than originally thought. Until these discoveries, the role of IL-12 in modulating cellular immune responses had been overestimated due to the belief that the IL-12 p40 subunit was unique to IL-12. However, because p40 is shared between IL-12 and IL-23, it would be expected that p40(-/-) mice are doubly deficient in IL-12 and IL-23. Indeed, the essential role previously attributed to IL-12 in experimental autoimmune encephalitis during studies of p40(-/-) mice has been shown to be due to IL-23 instead. The newest addition to the IL-12 cytokine family, IL-27, has unique features as well. Its specific action on naive CD4+ T cells in both mice and humans appears to distinguish it from the other IL-12 family members. Although related, the IL-12 family of cytokines and their receptors have distinct patterns of expression and unique effects on developing immune responses. This review summarises much of the pertinent literature on the IL-12 cytokine family and provides predictions regarding their potential therapeutic roles based on what has been learned about their functions in vitro and in vivo in gene-deficient mice.
authors.affiliation: Laboratory of Cell Biology, Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Cordoba-Rodriguez
authors.forename: David M
authors.initials: DM
authors.lastname: Frucht
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000502:physiology
chemical_list: C508840:IL23A protein, human; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; C464565:MYDGF protein, human; D011994:Recombinant Proteins; D018664:Interleukin-12