The oncoprotein TBX3 is controlling severity in experimental arthritis
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 e...
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13075-018-1797-3 |
| _version_ | 1818571848354365440 |
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| author | Samra Sardar Alish Kerr Daniëlle Vaartjes Emilie Riis Moltved Edita Karosiene Ramneek Gupta Åsa Andersson |
| author_facet | Samra Sardar Alish Kerr Daniëlle Vaartjes Emilie Riis Moltved Edita Karosiene Ramneek Gupta Åsa Andersson |
| author_sort | Samra Sardar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T18:49:41Z |
| format | Article |
| id | doaj.art-0ba8783808614096acef7fea01ca1999 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-14T18:49:41Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-0ba8783808614096acef7fea01ca19992022-12-21T22:51:17ZengBMCArthritis Research & Therapy1478-63622019-01-0121111710.1186/s13075-018-1797-3The oncoprotein TBX3 is controlling severity in experimental arthritisSamra Sardar0Alish Kerr1Daniëlle Vaartjes2Emilie Riis Moltved3Edita Karosiene4Ramneek Gupta5Åsa Andersson6Section for Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of CopenhagenSection for Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of CopenhagenSection for Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of CopenhagenSection for Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of CopenhagenDepartment of Bio and Health Informatics, Kemitorvet 208, Technical University of DenmarkDepartment of Bio and Health Informatics, Kemitorvet 208, Technical University of DenmarkSection for Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of CopenhagenAbstract 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.http://link.springer.com/article/10.1186/s13075-018-1797-3Collagen-induced arthritisTranscriptional regulationTBX3TBX5BiomarkerEae39r |
| spellingShingle | Samra Sardar Alish Kerr Daniëlle Vaartjes Emilie Riis Moltved Edita Karosiene Ramneek Gupta Åsa Andersson The oncoprotein TBX3 is controlling severity in experimental arthritis Arthritis Research & Therapy Collagen-induced arthritis Transcriptional regulation TBX3 TBX5 Biomarker Eae39r |
| title | The oncoprotein TBX3 is controlling severity in experimental arthritis |
| title_full | The oncoprotein TBX3 is controlling severity in experimental arthritis |
| title_fullStr | The oncoprotein TBX3 is controlling severity in experimental arthritis |
| title_full_unstemmed | The oncoprotein TBX3 is controlling severity in experimental arthritis |
| title_short | The oncoprotein TBX3 is controlling severity in experimental arthritis |
| title_sort | oncoprotein tbx3 is controlling severity in experimental arthritis |
| topic | Collagen-induced arthritis Transcriptional regulation TBX3 TBX5 Biomarker Eae39r |
| url | http://link.springer.com/article/10.1186/s13075-018-1797-3 |
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