The oncoprotein TBX3 is controlling severity in experimental arthritis

Samra Sardar, Alish Kerr, Daniëlle Vaartjes, Emilie Riis Moltved, Edita Karosiene, Ramneek Gupta, Åsa Andersson*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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. 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. 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. 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.
Original languageEnglish
Article number16
JournalArthritis Research & Therapy
Volume21
Issue number1
Number of pages17
ISSN1478-6354
DOIs
Publication statusPublished - 2019

Keywords

  • Biomarker
  • Collagen-induced arthritis
  • Eae39r
  • TBX3
  • TBX5
  • Transcriptional regulation

Cite this

Sardar, S., Kerr, A., Vaartjes, D., Moltved, E. R., Karosiene, E., Gupta, R., & Andersson, Å. (2019). The oncoprotein TBX3 is controlling severity in experimental arthritis. Arthritis Research & Therapy, 21(1), [16]. https://doi.org/10.1186/s13075-018-1797-3
Sardar, Samra ; Kerr, Alish ; Vaartjes, Daniëlle ; Moltved, Emilie Riis ; Karosiene, Edita ; Gupta, Ramneek ; Andersson, Åsa. / The oncoprotein TBX3 is controlling severity in experimental arthritis. In: Arthritis Research & Therapy. 2019 ; Vol. 21, No. 1.
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abstract = "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. 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. 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. 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.",
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Sardar, S, Kerr, A, Vaartjes, D, Moltved, ER, Karosiene, E, Gupta, R & Andersson, Å 2019, 'The oncoprotein TBX3 is controlling severity in experimental arthritis', Arthritis Research & Therapy, vol. 21, no. 1, 16. https://doi.org/10.1186/s13075-018-1797-3

The oncoprotein TBX3 is controlling severity in experimental arthritis. / Sardar, Samra; Kerr, Alish; Vaartjes, Daniëlle; Moltved, Emilie Riis; Karosiene, Edita; Gupta, Ramneek; Andersson, Åsa.

In: Arthritis Research & Therapy, Vol. 21, No. 1, 16, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

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AU - Sardar, Samra

AU - Kerr, Alish

AU - Vaartjes, Daniëlle

AU - Moltved, Emilie Riis

AU - Karosiene, Edita

AU - Gupta, Ramneek

AU - Andersson, Åsa

PY - 2019

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AB - 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. 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. 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. 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.

KW - Biomarker

KW - Collagen-induced arthritis

KW - Eae39r

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