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

Matteo Vecellio; Carla J Cohen; Amity R Roberts; Paul B Wordsworth; Tony J Kenna

doi:10.3389/fimmu.2018.03132

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.

Authors

Matteo Vecellio^{1

2

3}, Carla J Cohen^{1

2

3}, Amity R Roberts⁴, Paul B Wordsworth^{1

2

3}, Tony J Kenna^{5

6}

Affiliations

¹ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.
² Oxford Musculoskeletal Biomedical Research Unit, National Institute for Health Research, Oxford, United Kingdom.
³ Oxford Comprehensive Biomedical Research Centre, Botnar Research Centre, National Institute for Health Research, Nuffield Orthopaedic Centre, Oxford, United Kingdom.
⁴ Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
⁵ Translational Research Institute, Princess Alexandra Hospital, Brisbane, QLD, Australia.
⁶ Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding