title: The IL-12 family of cytokines in infection, inflammation and autoimmune disorders.
abstract: Cytokines are critical coordinators of the immune response necessary for resolving bacterial and viral assaults on the immune system. In particular, the IL-12 family of cytokines are key players in the regulation of T cell responses. These responses are orchestrated by monocytes, macrophages, and dendritic cells which produce the members of the IL-12 family of cytokines in response to infection. IL-27 and IL-23 are two cytokines that are related to IL-12; these cytokines share homology at the subunit, receptor, and signalling levels. IL-12 is composed of p35 and p40 subunits, which, when combined together form the bioactive IL-12p70. IL-23 is composed of the IL-12p40 subunit as well as the IL-23p19 subunit, which shares homology with IL-12p35. IL-27 is composed of EBI3 and p28. These three cytokines activate similar members of the JAK/STAT signalling pathways as a result of homology in their receptor components. Production of these cytokines by activated monocytes, macrophages, and dendritic cells results in the activation and differentiation of T cells. In spite of their similarity, each of these cytokines has specific roles in the regulation of immune responses. IL-12 is required for the induction of IFN-gamma production, critical for the induction of Th1 cells. IL-27 has been shown to play a role in the induction of Th1 cells from naive T cells, whereas IL-23 has been demonstrated to play a key role in the induction of the newly described Th17 cells. Recently, a novel heterodimeric and anti-inflammatory cytokine composed of the IL-12p35 and EBI3 subunits has been identified as IL-35. The biological properties of the IL-12 family of cytokines, the signalling pathways mediated by these cytokines and their role in infection, inflammation, and autoimmune diseases will be the focus of this review.
authors.affiliation: Department of Microbiology and Immunology, Queen's University, Kingston ON, Canada.
authors.forename: Katrina
authors.initials: K
authors.lastname: Gee
authors.forename: Christina
authors.initials: C
authors.lastname: Guzzo
authors.forename: Nor Fazila
authors.initials: NF
authors.lastname: Che Mat
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D019496:Cancer Vaccines; D006801:Humans; D007111:Immunity, Cellular; D007239:Infections / Q000276:immunology; D007249:Inflammation; D018664:Interleukin-12 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D053759:Interleukin-23 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D050791:STAT Transcription Factors; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D019496:Cancer Vaccines; D053759:Interleukin-23; D007378:Interleukins; C464565:MYDGF protein, human; D050791:STAT Transcription Factors; C532417:interleukin-35, human; D018664:Interleukin-12