Involvement of the IL-23/IL-17 axis and the Th17/Treg balance in the pathogenesis and control of autoimmune arthritis

Cytokine. 2015 Jul;74(1):54-61. doi: 10.1016/j.cyto.2014.11.020. Epub 2015 Jan 13.

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.

Keywords: Arthritis; Interleukin-17; Interleukin-23; Regulatory T cell; T helper 17.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arthritis / immunology*
  • Arthritis / physiopathology
  • Arthritis / therapy
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / physiopathology
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / physiopathology
  • Arthritis, Rheumatoid / therapy
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / physiopathology
  • Autoimmune Diseases / therapy
  • Humans
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukin-23 / immunology*
  • Interleukin-23 / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Th1-Th2 Balance
  • Th17 Cells / immunology*
  • Th17 Cells / pathology

Substances

  • IL17A protein, human
  • Interleukin-17
  • Interleukin-23