The oncoprotein TBX3 is controlling severity in experimental arthritis

Arthritis Res Ther. 2019 Jan 10;21(1):16. doi: 10.1186/s13075-018-1797-3.

Abstract

Background: Development of autoimmune diseases is the result of a complex interplay between hereditary and environmental factors, with multiple genes contributing to the pathogenesis in human disease and in experimental models for disease. The T-box protein 3 is a transcriptional repressor essential during early embryonic development, in the formation of bone and additional organ systems, and in tumorigenesis.

Methods: With the aim to find novel genes important for autoimmune inflammation, we have performed genetic studies of collagen-induced arthritis (CIA), a mouse experimental model for rheumatoid arthritis.

Results: We showed that a small genetic fragment on mouse chromosome 5, including Tbx3 and three additional protein-coding genes, is linked to severe arthritis and high titers of anti-collagen antibodies. Gene expression studies have revealed differential expression of Tbx3 in B cells, where low expression was accompanied by a higher B cell response upon B cell receptor stimulation in vitro. Furthermore, we showed that serum TBX3 levels rise concomitantly with increasing severity of CIA.

Conclusions: From these results, we suggest that TBX3 is a novel factor important for the regulation of gene transcription in the immune system and that genetic polymorphisms, resulting in lower expression of Tbx3, are contributing to a more severe form of CIA and high titers of autoantibodies. We also propose TBX3 as a putative diagnostic biomarker for rheumatoid arthritis.

Keywords: Biomarker; Collagen-induced arthritis; Eae39r; TBX3; TBX5; Transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / genetics*
  • Arthritis, Experimental / metabolism*
  • Arthritis, Experimental / pathology
  • Cattle
  • Cells, Cultured
  • Male
  • Mice
  • Mice, Congenic
  • Mice, Transgenic
  • Severity of Illness Index*
  • T-Box Domain Proteins / biosynthesis*
  • T-Box Domain Proteins / genetics*

Substances

  • T-Box Domain Proteins
  • Tbx3 protein, mouse