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Your search keyword '"HOLMDAHL, RIKARD"' showing total 10 results
Start Over Author "HOLMDAHL, RIKARD" Journal plos one
10 results on '"HOLMDAHL, RIKARD"'

1. Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis

Author

Tengvall, Sara, Eneljung, Tove, Jirholt, Pernilla, Turesson, Olof, Wing, Kajsa, Holmdahl, Rikard, Kihlberg, Jan, Stern, Anna, Martensson, Inga-Lill, Henningsson, Louise, Gustafsson, Kenth, and Gjertsson, Inger

Subjects
musculoskeletal diseases, Male, Medicin och hälsovetenskap, B Cells, Physiology, Immune Cells, Cell Lines, T-Lymphocytes, Immunology, lcsh:Medicine, Antigen-Presenting Cells, Research and Analysis Methods, Medical and Health Sciences, Antibodies, Lymphatic System, White Blood Cells, Mice, Rheumatology, Animal Cells, Immune Physiology, Medicine and Health Sciences, Immune Tolerance, Animals, Antigens, lcsh:Science, Antibody-Producing Cells, Collagen Type II, B-Lymphocytes, Blood Cells, Hybridomas, T Cells, Arthritis, lcsh:R, Biology and Life Sciences, Cell Biology, Regulatory T cells, Genetic Therapy, Flow Cytometry, Arthritis, Experimental, Mice, Inbred DBA, Cytokines, lcsh:Q, Biological Cultures, Lymph Nodes, Cellular Types, Anatomy, Spleen, Research Article
Abstract

Here, we investigate induction of immunological tolerance by lentiviral based gene therapy in a mouse model of rheumatoid arthritis, collagen II-induced arthritis (CIA). Targeting the expression of the collagen type II (CII) to antigen presenting cells (APCs) induced antigen-specific tolerance, where only 5% of the mice developed arthritis as compared with 95% of the control mice. In the CII-tolerized mice, the proportion of Tregs as well as mRNA expression of SOCS1 (suppressors of cytokine signaling 1) increased at day 3 after CII immunization. Transfer of B cells or non-B cell APC, as well as T cells, from tolerized to naive mice all mediated a certain degree of tolerance. Thus, sustainable tolerance is established very early during the course of arthritis and is mediated by both B and non-B cells as APCs. This novel approach for inducing tolerance to disease specific antigens can be used for studying tolerance mechanisms, not only in CIA but also in other autoimmune diseases.

Published
2016

2. Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat

Author

Tuncel, Jonatan, primary, Haag, Sabrina, additional, Hoffmann, Markus H., additional, Yau, Anthony C. Y., additional, Hultqvist, Malin, additional, Olofsson, Peter, additional, Bäcklund, Johan, additional, Nandakumar, Kutty Selva, additional, Weidner, Daniela, additional, Fischer, Anita, additional, Leichsenring, Anna, additional, Lange, Franziska, additional, Haase, Claus, additional, Lu, Shemin, additional, Gulko, Percio S., additional, Steiner, Günter, additional, and Holmdahl, Rikard, additional

Published
2016
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10. Deficient Production of Reactive Oxygen Species Leads to Severe Chronic DSS-Induced Colitis in Ncf1/p47phox-Mutant Mice.

Author

Rodrigues-Sousa, Tiago, Ladeirinha, Ana Filipa, Santiago, Ana Raquel, Carvalheiro, Helena, Raposo, Bruno, Alarcão, Ana, Cabrita, António, Holmdahl, Rikard, Carvalho, Lina, and Souto-Carneiro, M. Margarida

Subjects
OXYGEN in the body, GENETIC mutation, LABORATORY mice, DEXTRAN sulfate, IMMUNOHISTOCHEMISTRY, COLITIS, LYMPHOCYTES
Abstract

Background: Colitis is a common clinical complication in chronic granulomatous disease (CGD), a primary immunodeficiency caused by impaired oxidative burst. Existing experimental data from NADPH-oxidase knockout mice propose contradictory roles for the involvement of reactive oxygen species in colitis chronicity and severity. Since genetically controlled mice with a point-mutation in the Ncf1 gene are susceptible to chronic inflammation and autoimmunity, we tested whether they presented increased predisposition to develop chronic colitis. Methods: Colitis was induced in Ncf1-mutant and wild-type mice by a 1st 7-days cycle of dextran sulfate sodium (DSS), intercalated by a 7-days resting period followed by a 2nd 7-days DSS-cycle. Cytokines were quantified locally in the colon inflammatory infiltrates and in the serum. Leukocyte infiltration and morphological alterations of the colon mucosa were assessed by immunohistochemistry. Results: Clinical scores demonstrated a more severe colitis in Ncf1-mutant mice than controls, with no recovery during the resting period and a severe chronic colitis after the 2nd cycle, confirmed by histopathology and presence of infiltrating neutrophils, macrophages, plasmocytes and lymphocytes in the colon. Severe colitis was mediated by increased local expression of cytokines (IL-6, IL-10, TNF-α, IFN-γ and IL-17A) and phosphorylation of Leucine-rich repeat kinase 2 (LRRK2). Serological cytokine titers of those inflammatory cytokines were more elevated in Ncf1-mutant than control mice, and were accompanied by systemic changes in functional subsets of monocytes, CD4+T and B cells. Conclusion: This suggests that an ineffective oxidative burst leads to severe chronic colitis through local accumulation of peroxynitrites, pro-inflammatory cytokines and lymphocytes and systemic immune deregulation similar to CGD. [ABSTRACT FROM AUTHOR]

Published
2014
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