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Cystatin C influenc...
Cystatin C influences the autoimmune but not inflammatory response to cartilage type II collagen leading to chronic arthritis development
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- Bäcklund, A. (author)
- Karolinska Institutet,Karolinska Institute, Stockholm, Sweden
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- Holmdahl, M. (author)
- Karolinska Institute, Stockholm, Sweden
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- Mattsson, Ragnar (author)
- Lund University,Lunds universitet,Medicinska fakulteten,Faculty of Medicine,Lund University, Lund, Sweden
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- Håkansson, Katarina (author)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Lund University, Lund, Sweden; Novo Nordisk A/S, Novo Nordisk Park, Måløv, Sweden
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- Lindström, Veronica (author)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Lund University, Lund, Sweden
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- Nandakumar, Kutty Selva, 1965- (author)
- Karolinska Institutet,Karolinska Institute, Stockholm, Sweden
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- Grubb, Anders (author)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Lund University, Lund, Sweden
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- Holmdahl, R. (author)
- Karolinska Institutet,Karolinska Institute, Stockholm, Sweden
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(creator_code:org_t)
- 2011-03-28
- 2011
- English.
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 13
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Abstract
Subject headings
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- INTRODUCTION: Collagen-induced arthritis (CIA) is a mouse model for rheumatoid arthritis (RA) and is induced after immunization with type II collagen (CII). CIA, like RA, is an autoimmune disease leading to destruction of cartilage and joints, and both the priming and inflammatory phases have been suggested to be dependent on proteases. In particular, the cysteine proteases have been proposed to be detrimental to the arthritic process and even immunomodulatory. A natural inhibitor of cysteine proteases is cystatin C. METHODS: Cystatin C-deficient, sufficient and heterozygous mice were tested for onset, incidence and severity of CIA. The effect of cystatin C-deficiency was further dissected by testing the inflammatory effector phase of CIA; that is, collagen antibody-induced arthritis model and priming phase, that is, T cell response both in vivo and in vitro. In addition, in order to determine the importance of T cells and antigen-presenting cells (APCs), these cell populations were separated and in vitro T cell responses determined in a mixed co-culture system. Finally, flow cytometry was used in order to further characterize cell populations in cystatin C-deficient mice. RESULTS: Here, we show that mice lacking cystatin C, develop arthritis at a higher incidence and an earlier onset than wild-type controls. Interestingly, when the inflammatory phase of CIA was examined independently from immune priming then cystatin C-deficiency did not enhance the arthritis profile. However, in line with the enhanced CIA, there was an increased T cell and B cell response as delayed-type hypersensitivity reaction and anti-CII antibody titers were elevated in the cystatin C-deficient mice after immunization. In addition, the ex vivo naive APCs from cystatin C-deficient mice had a greater capacity to stimulate T cells. Interestingly, dendritic cells had a more activated phenotype in naive cystatin C-deficient mice. CONCLUSIONS: The lack of cystatin C enhances CIA and primarily affects in vivo priming of the immune system. Although the mechanism of this is still unknown, we show evidence for a more activated APC compartment, which would elevate the autoimmune response towards CII, thus resulting in an enhanced development of chronic arthritis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Animals
- Antigen Presentation/immunology
- Arthritis
- Experimental/genetics/*immunology
- Arthritis
- Rheumatoid/genetics/*immunology
- Autoantibodies/immunology
- Autoantigens/immunology
- Autoimmunity/genetics/*immunology
- Cell Separation
- Collagen Type II/immunology/toxicity
- Cystatin C/genetics/*immunology
- Flow Cytometry
- Hypersensitivity
- Delayed/genetics/immunology
- Inflammation/genetics/*immunology
- Lymphocyte Activation/immunology
- Mice
- Mice
- Knockout
- T-Lymphocytes/immunology
Publication and Content Type
- ref (subject category)
- art (subject category)
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