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Publications (10 of 12) Show all publications
Andersson, Å. & Sardar, S. (2019). A transcriptional regulator controlling severity in experimental arthritis. Paper presented at Annual European Congress of Rheumatology, EULAR 2019, Madrid, Spain, June 12-15, 2019. Annals of the Rheumatic Diseases, 78(Suppl. 2), 667-667, Article ID FRI0011.
Open this publication in new window or tab >>A transcriptional regulator controlling severity in experimental arthritis
2019 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, no Suppl. 2, p. 667-667, article id FRI0011Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

Background: Susceptibility to Rheumatoid Arthritis (RA) is dependent on complex interactions among genetic and environmental factors. Protein candidates and their role in pathways leading to chronic inflammation of the joints, in addition to their potential as drug targets, can be revealed with the help of experimental models for disease (1). From the results of functional genetic studies, we have recently shown that the T-box gene, TBX3, is a candidate gene in Collagen Induced Arthritis (CIA), an experimental model for RA (2). TBX3 encodes a transcriptional regulator involved in differentiation of several organs, including bone, during embryonic development. It has, in addition, been demonstrated important in oncogenesis (3). Our studies suggest that TBX3 has a role in B-cell activation and is important for the severity of disease in the CIA model (2). Objectives: The objective of this project is to understand the role for the transcriptional regulator TBX3 in development of RA. Methods: Bioinformatics based comparative studies of mouse and human alleles in the regulatory region of TBX3. CRISPR/Cas9-introduced deletions and base modifications in human B-cell lines. Activation of genetically modified B-cells in vitro, followed by analyses of proliferative response and antibody production. Results: Studies of CIA development in mice with single nucleotide polymorphisms (SNPs) in the regulatory region of Tbx3 revealed a significant difference in severity of arthritis. In line with this, the anti-collagen type II antibody titers were shown substantially higher in mice with more severe arthritis, even before onset of disease. In addition, preliminary data shows that the proliferative response to Type II collagen upon re-challenge of lymph node cells in vitro is higher in these mice, suggesting a more active response to the disease-inducing antigen. Because the TBX3 gene is conserved between mouse and human, we are investigating whether similar genetic variations are found in the regulatory region of the human TBX3 gene and whether the putative genetic variation would lead to a distinct B-cell phenotype upon activation in vitro. Conclusion: We suggest that the oncoprotein TBX3 is a novel candidate contributing to disease severity in experimental arthritis. Investigations of genetic variation in the TBX3 gene and its role in the activation of human B-cells will reveal whether this protein is a candidate for influencing also development of RA.

Place, publisher, year, edition, pages
London, UK: BMJ Publishing Group Ltd, 2019
Keywords
Rheumatoid Arthritis, Collagen-induced arthritis, TBX3, transcriptional regulator, biomarker
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:hh:diva-39950 (URN)10.1136/annrheumdis-2019-eular.7057 (DOI)000472207102055 ()
Conference
Annual European Congress of Rheumatology, EULAR 2019, Madrid, Spain, June 12-15, 2019
Available from: 2019-06-23 Created: 2019-06-23 Last updated: 2019-09-10Bibliographically approved
Aksel Jacobsen, F. & Andersson, Å. (2019). Inhibitors of intracellular enzymes for treatment of multiple sclerosis. Atlas of Science
Open this publication in new window or tab >>Inhibitors of intracellular enzymes for treatment of multiple sclerosis
2019 (English)In: Atlas of ScienceArticle, review/survey (Other (popular science, discussion, etc.)) Published
Place, publisher, year, edition, pages
AoS Nordic AB, 2019
Keywords
MS, EAE, tyrosin kinase inhibitors, lymphocytes
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:hh:diva-39376 (URN)
Available from: 2019-05-17 Created: 2019-05-17 Last updated: 2019-08-06Bibliographically approved
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), Article ID 16.
Open this publication in new window or tab >>The oncoprotein TBX3 is controlling severity in experimental arthritis
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2019 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 21, no 1, article id 16Article in journal (Refereed) Published
Abstract [en]

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 as well as 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, a mouse experimental model for Rheumatoid Arthritis.

Results: We show 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 show 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 collagen-induced arthritis and high titers of autoantibodies. We also propose TBX3 as a putative diagnostic biomarker for rheumatoid arthritis.

Place, publisher, year, edition, pages
London: BioMed Central, 2019
Keywords
Collagen-induced arthritis, transcriptional regulation, TBX3, TBX5, biomarker, Eae39r
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:hh:diva-38630 (URN)10.1186/s13075-018-1797-3 (DOI)30630509 (PubMedID)
Note

Funding: The Danish Rheumatism Association, The AP Møller Research grant for Medical Science and The Oticon foundation

Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2019-01-14Bibliographically approved
Aksel Jacobsen, F., Scherer, A. N., Mouritsen, J., Bragadóttir, H., Bäckström, B. T., Sardar, S., . . . Andersson, Å. (2018). A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation. Journal of Neuroimmune Pharmacology, 13(2), 265-276
Open this publication in new window or tab >>A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation
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2018 (English)In: Journal of Neuroimmune Pharmacology, ISSN 1557-1890, E-ISSN 1557-1904, Vol. 13, no 2, p. 265-276Article in journal (Refereed) Published
Abstract [en]

Multiple sclerosis is a neuroinflammatory degenerative disease, caused by activated immune cells infiltrating the CNS. The disease etiology involves both genetic and environmental factors. The mouse genetic locus, Eae27, linked to disease development in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis, was studied in order to identify contributing disease susceptibility factors and potential drug targets for multiple sclerosis. Studies of an Eae27 congenic mouse strain, revealed that genetic variation within Eae27 influences EAE development. The Abl2 gene, encoding the non-receptor tyrosine kinase Arg, is located in the 4,1 megabase pair long Eae27 region. The Arg protein plays an important role in cellular regulation and is, in addition, involved in signaling through the B- and T-cell receptors, important for the autoimmune response. The presence of a single nucleotide polymorphism causing an amino acid change in a near actin-interacting domain of Arg, in addition to altered lymphocyte activation in the congenic mice upon immunization with myelin antigen, makes Abl2/Arg a candidate gene for EAE. Here we demonstrate that the non-synonymous SNP does not change Arg’s binding affinity for F-actin but suggest a role for Abl kinases in CNS inflammation pathogenesis by showing that pharmacological inhibition of Abl kinases ameliorates EAE, but not experimental arthritis. © 2018 The Author(s)

Place, publisher, year, edition, pages
New York, NY: Springer-Verlag New York, 2018
Keywords
Abl kinase, Arg, Eae27, Experimental autoimmune encephalomyelitis, Imatinib
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:hh:diva-36440 (URN)10.1007/s11481-018-9783-8 (DOI)29550892 (PubMedID)2-s2.0-85044043378 (Scopus ID)
Note

Funding: Novo Nordisk, Denmark; SHARE (Synergy in human and animal research) University of Copenhagen; The Warwara Larsen Foundation, The Carlsberg Foundation; The Karen A. Tolstrup Foundation; The A.P. Møller Foundation.

Available from: 2018-03-16 Created: 2018-03-16 Last updated: 2018-05-03Bibliographically approved
Andersson, Å. (2018). Abl-tyrosinkinaser och multipel skleros. BestPractice, 6(24), 14-16
Open this publication in new window or tab >>Abl-tyrosinkinaser och multipel skleros
2018 (Swedish)In: BestPractice, Vol. 6, no 24, p. 14-16Article, review/survey (Other academic) Published
Place, publisher, year, edition, pages
Uppsala: , 2018
Keywords
Multipel Skleros, Experimentell Autoimmun Encefalomyelit, Abl2, imatinib, tyrosinkinashämmare
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:hh:diva-38281 (URN)
Available from: 2018-12-05 Created: 2018-12-05 Last updated: 2018-12-06Bibliographically approved
Sardar, S., Kanne, K. & Andersson, Å. (2018). Analysis of polymorphisms in the mediator complex subunit 13-like (Med13L) gene in the context of immune function and development of experimental arthritis. Archivum Immunologiae et Therapiae Experimentalis, 66(5), 365-377
Open this publication in new window or tab >>Analysis of polymorphisms in the mediator complex subunit 13-like (Med13L) gene in the context of immune function and development of experimental arthritis
2018 (English)In: Archivum Immunologiae et Therapiae Experimentalis, ISSN 0004-069X, E-ISSN 1661-4917, Vol. 66, no 5, p. 365-377Article in journal (Refereed) Published
Abstract [en]

The Mediator complex subunit 13-like (MED13L) protein is part of the multi-protein mediator complex and plays an important role in gene transcription. Polymorphisms in the MED13L gene have been linked to congenital heart anomalies and intellectual disabilities. Despite recent evidence of indirect links of MED13L to cytokine release and inflammation, impact of genetic variations in MED13L on immune cells remains unexplored. The B10.RIII and RIIIS/J mouse strains vary in susceptibility to induced experimental autoimmune disease models. From sequencing data of the two mouse strains, we identified six polymorphisms in the coding regions of Med13l. By using congenic mice, we studied the effect of these polymorphisms on immune cell development and function along with susceptibility to collagen-induced arthritis, an animal model for Rheumatoid Arthritis (RA). Combining in vivo disease data, in vitro functional data, and computational analysis of the reported non-synonymous polymorphisms, we report that genetic polymorphisms in Med13l do not affect the immune phenotype in these mice and are predicted to be non-disease associated. © The Author(s) 2018

Place, publisher, year, edition, pages
Basel: Springer, 2018
Keywords
MED13L, THRAP2, mediator complex, Collagen-induced arthritis, Rheumatoid Arthritis, congenic mice
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:hh:diva-36795 (URN)10.1007/s00005-018-0516-8 (DOI)29951696 (PubMedID)2-s2.0-85049072770 (Scopus ID)
Note

This work was supported by The Danish Rheumatism Association, The AP Møller Research grant for Medical Science, and The Oticon foundation.

Available from: 2018-05-21 Created: 2018-05-21 Last updated: 2018-09-27Bibliographically approved
Sardar, S., Alish, K., Vaartjes, D., Voetmann, M. E., Moltved, E. R. & Andersson, Å. (2017). A novel candidate for genetic control of Collagen Induced Arthritis is involved in transcriptional regulation of B-cell proliferation. In: : . Paper presented at 8th International Forum for RA (IFRA), September 23-26, 2017, Karolinska Institute, Stockholm, Sweden.
Open this publication in new window or tab >>A novel candidate for genetic control of Collagen Induced Arthritis is involved in transcriptional regulation of B-cell proliferation
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2017 (English)Conference paper, Poster (with or without abstract) (Other academic)
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:hh:diva-35895 (URN)
Conference
8th International Forum for RA (IFRA), September 23-26, 2017, Karolinska Institute, Stockholm, Sweden
Available from: 2017-12-15 Created: 2017-12-15 Last updated: 2018-06-12Bibliographically approved
Sardar, S., Vartjes, D., Voetmann, M. & Andersson, Å. (2017). Novel candidates for genetic control of Collagen INduced Arthritis are involved in transcriptional regulation of B-cell proliferation. In: : . Paper presented at Federation of Clinical Immunology Societies (FOCIS) 2017, Chicago, IL, USA, Jun 14-17, 2017.
Open this publication in new window or tab >>Novel candidates for genetic control of Collagen INduced Arthritis are involved in transcriptional regulation of B-cell proliferation
2017 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:hh:diva-35835 (URN)
Conference
Federation of Clinical Immunology Societies (FOCIS) 2017, Chicago, IL, USA, Jun 14-17, 2017
Available from: 2017-12-13 Created: 2017-12-13 Last updated: 2018-04-17Bibliographically approved
Jacobsen, F. A., Hulst, C., Bäckström, T., Koleske, A. J. & Andersson, Å. (2016). Arg Deficiency Does not Influence the Course of Myelin Oligodendrocyte Glycoprotein (MOG35-55)-induced Experimental Autoimmune Encephalomyelitis. Journal of Clinical & Cellular Immunology, 7(3), Article ID 1000420.
Open this publication in new window or tab >>Arg Deficiency Does not Influence the Course of Myelin Oligodendrocyte Glycoprotein (MOG35-55)-induced Experimental Autoimmune Encephalomyelitis
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2016 (English)In: Journal of Clinical & Cellular Immunology, ISSN 2155-9899, E-ISSN 2155-9899, Vol. 7, no 3, article id 1000420Article in journal (Refereed) Published
Abstract [en]

Background: Inhibition of Abl kinases has an ameliorating effect on the rodent model for multiple sclerosis, experimental autoimmune encephalomyelitis, and arrests lymphocyte activation. The family of Abl kinases consists of the Abl1/Abl and Abl2/Arg tyrosine kinases. While the Abl kinase has been extensively studied in immune activation, roles for Arg are incompletely characterized. To investigate the role for Arg in experimental autoimmune encephalomyelitis, we studied disease development in Arg-/- mice.

Methods: Arg-/- and Arg+/+ mice were generated from breeding of Arg+/- mice on the C57BL/6 background. Mice were immunized with the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide and disease development recorded. Lymphocyte phenotypes of wild type Arg+/+ and Arg-/- mice were studied by in vitro stimulation assays and flow cytometry.

Results: The breeding of Arg+/+ and Arg-/- mice showed skewing in the frequency of born Arg-/- mice. Loss of Arg function did not affect development of experimental autoimmune encephalomyelitis, but reduced the number of splenic B-cells in Arg-/- mice following immunization with MOG peptide.

Conclusions: Development of MOG-induced experimental autoimmune encephalomyelitis is not dependent on Arg, but Arg plays a role for the number of B cells in immunized mice. This might suggest a novel role for the Arg kinase in B-cell trafficking or regulation. Furthermore, the results suggest that Arg is important for normal embryonic development. © 2016 Jacobsen FA, et al.

Place, publisher, year, edition, pages
Los Angeles: OMICS, 2016
Keywords
Abelson related gene, Experimental autoimmune encephalomyelitis, Lymphocyte phenotypes, Genotype frequency
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:hh:diva-33668 (URN)10.4172/2155-9899.1000420 (DOI)
Note

Funding: Novo Nordisk, Denmark; SHARE (Synergy in human and animal research) Copenhagen University; The Warwara Larsen Foundation, The Carlsberg Foundation; The Karen A Tolstrup Foundation; The A.P. Møller Foundation.

Available from: 2017-04-04 Created: 2017-04-04 Last updated: 2018-04-17Bibliographically approved
Andersson, Å. & Aksel Jacobsen, F. (2016). B-cells and Inflammation in the Absence of the Abelson Related Gene (Arg). Journal of Clinical & Cellular Immunology, 7(6), Article ID 1000470.
Open this publication in new window or tab >>B-cells and Inflammation in the Absence of the Abelson Related Gene (Arg)
2016 (English)In: Journal of Clinical & Cellular Immunology, ISSN 2155-9899, E-ISSN 2155-9899, Vol. 7, no 6, article id 1000470Article in journal (Refereed) Published
Abstract [en]

The Abelson non-receptor tyrosine kinases, c-Abl and Arg, are important regulators of cellular processes in cancer, inflammation, infection, and neuronal dynamics. Recent research on the role for these kinases in processes involving interactions with the cytoskeleton or signaling molecules, may lead to further insight into the pathogenesis of a variety of disorders, including chronic inflammatory diseases. In a mouse model for multiple sclerosis, we recently reported that Arg deficient mice develop T-cell mediated autoimmune neuro-inflammation with the same severity as littermate controls, but display a different B-cell phenotype upon immunization. Here we comment on these results and discuss the role for Arg in B-cell activation and homeostasis.

Place, publisher, year, edition, pages
Los Angeles, CA: Omics Publishing Group, 2016
Keywords
Arg/Abl2, c-Abl, Experimental autoimmune encephalomyelitis (EAE), B-cells
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:hh:diva-32443 (URN)10.4172/2155-9899.1000470 (DOI)
Available from: 2016-11-18 Created: 2016-11-18 Last updated: 2018-04-17Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-4360-7710

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