Interleukin-12 and the regulation of innate resistance and adaptive immunity.
Interleukin-12 (IL-12) is a heterodimeric pro-inflammatory cytokine that induces the production of interferon-gamma (IFN-gamma), favours the differentiation of T helper 1 (T(H)1) cells and forms a link between innate resistance and adaptive immunity. Dendritic cells (DCs) and phagocytes produce IL-12 in response to pathogens during infection. Production of IL-12 is dependent on differential mechanisms of regulation of expression of the genes encoding IL-12, patterns of Toll-like receptor (TLR) expression and cross-regulation between the different DC subsets, involving cytokines such as IL-10 and type I IFN. Recent data, however, argue against an absolute requirement for IL-12 for T(H)1 responses. Our understanding of the relative roles of IL-12 and other factors in T(H)1-type maturation of both CD4+ and CD8+ T cells is discussed here, including the participation in this process of IL-23 and IL-27, two recently discovered members of the new family of heterodimeric cytokines.
Trinchieri
Giorgio
G
Laboratory for Immunological Research, Schering-Plough Research Institute, 27 Chemin des Peupliers, B.P. 11, 69571 Dardilly, France. Giorgio.Trinchieri@spcorp.com
D000222:Adaptation, Physiological; D000818:Animals; D002454:Cell Differentiation; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007239:Infections / Q000276:immunology; D018664:Interleukin-12 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000276:immunology; D018448:Models, Immunological; D015394:Molecular Structure; D009369:Neoplasms / Q000276:immunology; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D053707:Receptors, Interleukin-12; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology
C508840:IL23A protein, human; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12