From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation revisited.
Protracted inflammation leading to dysregulation of effector T-cell responses represents a common feature of a wide range of autoimmune diseases. The interleukin-12 (IL-12)/T-helper 1 (Th1) pathway was thought to be responsible for the pathogenesis of multiple chronic inflammatory diseases, including psoriasis, inflammatory bowel disease, arthritis, or multiple sclerosis, mainly through their production of interferon-gamma and its effects on macrophage activation and chemokine production. However, this initial concept of T-cell-mediated chronic inflammation required an adjustment with the discovery of an IL-12-related cytokine, designated IL-23. IL-23 was rapidly recognized for its involvement in the establishment of chronic inflammation and in the development of a Th cell subset producing IL-17, designated Th17, which is distinct from the previously reported Th1 and Th2 populations. This review aims to describe the characterization of IL-23 and its receptor, its biological activities, as well as its involvement in the development of human Th17 cells and autoimmunity.
Boniface
Katia
K
Department of Immunology, Schering-Plough Biopharma (Formerly DNAX Research), Palo Alto, CA 94304, USA.
Blom
Bianca
B
Liu
Yong-Jun
YJ
de Waal Malefyt
René
R
D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D018664:Interleukin-12