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

Brian Astry, Shivaprasad H. Venkatesha, Kamal D. Moudgil

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)54-61
Number of pages8
JournalCytokine
Volume74
Issue number1
DOIs
StatePublished - Jul 1 2015

Bibliographical note

Funding Information:
This work was supported by R01 AT004321 (KDM) and F31 AT007278 (BA) from NIH/NCCAM.

Keywords

  • Arthritis
  • Interleukin-17
  • Interleukin-23
  • Regulatory T cell
  • T helper 17

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