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The oncoprotein TBX3 is controlling severity in experimental arthritis.
Sardar, Samra; Kerr, Alish; Vaartjes, Daniëlle; Moltved, Emilie Riis; Karosiene, Edita; Gupta, Ramneek; Andersson, Åsa.
Afiliación
  • Sardar S; Section for Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • Kerr A; Present address: Nordic Bioscience A/S, Copenhagen, Denmark.
  • Vaartjes D; Section for Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • Moltved ER; Present address: Nuritas, Dublin, Ireland.
  • Karosiene E; Section for Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • Gupta R; Present address: Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Andersson Å; Section for Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Arthritis Res Ther ; 21(1): 16, 2019 01 10.
Article en En | MEDLINE | ID: mdl-30630509
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Índice de Severidad de la Enfermedad / Proteínas de Dominio T Box Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Arthritis Res Ther Asunto de la revista: REUMATOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Índice de Severidad de la Enfermedad / Proteínas de Dominio T Box Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Arthritis Res Ther Asunto de la revista: REUMATOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido