Insights into IL-23 biology: From structure to function

Cytokine Growth Factor Rev. 2015 Oct;26(5):569-78. doi: 10.1016/j.cytogfr.2015.07.005. Epub 2015 Jul 11.

Abstract

Interleukin (IL-)23 is a central cytokine controlling TH17 development. Overshooting IL-23 signaling contribute to autoimmune diseases. Moreover, GWAS studies have identified several SNPs within the IL-23 receptor, which are associated with autoimmune diseases. IL-23 is a member of the IL-12-type cytokine family and consists of IL-23p19 and p40. Within the IL-12 family, IL-12 and IL-23 share the p40 cytokine subunit and the IL-12Rβ1 as one chain of the receptor complex. For signaling, IL-23 triggers heterodimerization of IL-12Rβ1 and the IL-23R. Subsequently, signal transduction pathways including JAK/STAT, MAPK and PI3K are activated. Most studies have investigated the biological relevance of IL-23 in the development of TH17 cells and autoimmunity, whereas less is known about the molecular context of IL-23 biology. Therefore, we focused on IL-23 receptor complex assembly, signal transduction and functional relevance of IL-23R SNPs in the context of IL-23-inhibitory principles.

Keywords: IL-12Rβ1; IL-23 receptor; Interleukin 23; Signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Humans
  • Interleukin-23 / immunology*
  • Janus Kinases / immunology
  • MAP Kinase Signaling System / immunology*
  • Phosphatidylinositol 3-Kinases / immunology
  • Receptors, Interleukin / immunology*
  • Receptors, Interleukin-12 / immunology*
  • STAT Transcription Factors / immunology
  • Th17 Cells / immunology*
  • Th17 Cells / pathology

Substances

  • IL12RB1 protein, human
  • IL23R protein, human
  • Interleukin-23
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • STAT Transcription Factors
  • Phosphatidylinositol 3-Kinases
  • Janus Kinases