Stepwise regulation of TH1 responses in autoimmunity: IL-12-related cytokines and their receptors.
Interleukin (IL)-12 is a key cytokine of cell-mediated immune responses. Until recently, IL-12 was believed to be unique in its ability to induce the differentiation of naive T cells toward the TH1 phenotype and in its pathogenic activity, as shown in various disease models including inflammatory bowel disease. However, recently, 2 additional cytokines closely related to IL-12, IL-23 and IL-27, were discovered. Until then, the role of IL-12 was overestimated because it was believed that the p40 subunit was unique to IL-12. The discovery that IL-12 shares p40 with IL-23 and that IL-23 but not IL-12 is essential in models of chronic inflammation and autoimmunity led to a model in which IL-12 is essential to induce interferon-gamma-producing TH1 cells, whereas IL-23 mediates effector functions. The latest cytokine added to this cytokine family is IL-27. IL-27 has the unique feature to act on naive T cells, rendering them susceptible to IL-12 signaling. Thus, IL-27 may be essential for the early events of a cell-mediated immune response. This review focuses on these novel cytokines and their role in cell-mediated immune responses and discusses differences and common features within the family of IL-12-related cytokines.
Becker
Christoph
C
Laboratory of Immunology, I. Department of Medicine, University of Mainz, Germany.
Wirtz
Stefan
S
Neurath
Markus F
MF
D000818:Animals; D015551:Autoimmunity / Q000502:physiology; D016207:Cytokines / Q000276:immunology* / Q000502:physiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology* / Q000502:physiology; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000503:physiopathology; D018664:Interleukin-12 / Q000276:immunology* / Q000502:physiology; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000276:immunology / Q000502:physiology; D008297:Male; D051379:Mice; D011379:Prognosis; D018123:Receptors, Interleukin / Q000276:immunology* / Q000502:physiology; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology* / Q000502:physiology
D016207:Cytokines; C508840:IL23A protein, human; C508841:Il23a protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D018123:Receptors, Interleukin; D018664:Interleukin-12