RUNX3 and T-Bet in Immunopathogenesis of Ankylosing Spondylitis-Novel Targets for Therapy?

Front Immunol. 2019 Jan 10:9:3132. doi: 10.3389/fimmu.2018.03132. eCollection 2018.

Abstract

Susceptibility to ankylosing spondylitis (AS) is polygenic with more than 100 genes identified to date. These include HLA-B27 and the aminopeptidases (ERAP1, ERAP2, and LNPEPS), which are involved in antigen processing and presentation to T-cells, and several genes (IL23R, IL6R, STAT3, JAK2, IL1R1/2, IL12B, and IL7R) involved in IL23 driven pathways of inflammation. AS is also strongly associated with polymorphisms in two transcription factors, RUNX3 and T-bet (encoded by TBX21), which are important in T-cell development and function. The influence of these genes on the pathogenesis of AS and their potential for identifying drug targets is discussed here.

Keywords: ankylosing spondylitis; autoimmunity; functional genomics; inflammation; therapy.

Publication types

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

MeSH terms

  • Aminopeptidases / genetics
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Core Binding Factor Alpha 3 Subunit / antagonists & inhibitors
  • Core Binding Factor Alpha 3 Subunit / genetics*
  • Core Binding Factor Alpha 3 Subunit / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology*
  • HLA-B27 Antigen / genetics
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Molecular Targeted Therapy / methods
  • Polymorphism, Single Nucleotide
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin / metabolism
  • Spondylitis, Ankylosing / genetics
  • Spondylitis, Ankylosing / immunology*
  • T-Box Domain Proteins / antagonists & inhibitors
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / metabolism

Substances

  • Core Binding Factor Alpha 3 Subunit
  • HLA-B27 Antigen
  • Immunologic Factors
  • Interleukin-23
  • Receptors, Interleukin
  • Runx3 protein, human
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Aminopeptidases