title: Involvement of the IL-23/IL-17 axis and the Th17/Treg balance in the pathogenesis and control of autoimmune arthritis.
abstract: The T helper (Th) cell subsets are characterized by the type of cytokines produced and the master transcription factor expressed. Th1 cells participate in cell-mediated immunity, whereas Th2 cells promote humoral immunity. Furthermore, the two subsets can control each other. Thereby, Th1-Th2 balance offered a key paradigm in understanding the induction and regulation of immune pathology in autoimmune and other diseases. However, over the past decade, Th17 cells producing interleukin-17 (IL-17) have emerged as the major pathogenic T cell subset in many pathological conditions that were previously attributed to Th1 cells. In addition, the role of CD4+CD25+T regulatory cells (Treg) in controlling the activity of Th17 and other T cell subsets has increasingly been realized. Thereby, examination of the Th17/Treg balance in the course of autoimmune diseases has significantly advanced our understanding of the pathogenesis of these disorders. The differentiation of Th17 and Treg cells from naïve T cells is inter-related and controlled in part by the cytokine milieu. For example, transforming growth factor β (TGFβ) is required for Treg induction, whereas the same cytokine in the presence of IL-6 (or IL-1) promotes the differentiation of Th17. Furthermore, IL-23 plays a role in the maintenance of Th17. Accordingly, novel therapeutic approaches are being developed to target IL-23/IL-17 as well as to modulate the Th17/Treg balance in favor of immune regulation to control autoimmunity.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Astry
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Shivaprasad H
authors.initials: SH
authors.lastname: Venkatesha
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, United States. Electronic address: kmoudgil@som.umaryland.edu.
authors.forename: Kamal D
authors.initials: KD
authors.lastname: Moudgil
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D001169:Arthritis, Experimental / Q000276:immunology / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058408:Th1-Th2 Balance; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D053759:Interleukin-23
keywords: Arthritis; Interleukin-17; Interleukin-23; Regulatory T cell; T helper 17