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Mast cell chymase contributes to the antibody response and the severity of autoimmune arthritis

Sofia E. Magnusson^*, Gunnar Pejler, Sandra Kleinau^*,1,2 and Magnus Åbrink^,1,2

^* Department of Cell and Molecular Biology, Program for Molecular Immunology, and

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; and

Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden

²Correspondence: S.K., Uppsala University, Department of Cell and Molecular Biology, Program for Molecular Immunology, Biomedical Centre, Box 596, SE-751 24, Uppsala, Sweden. E-mail: sandra.kleinau{at}icm.uu.se; M.Å., Uppsala University, Department of Medical Biochemistry and Microbiology, Biomedical Centre, Box 582, SE-751 24, Uppsala, Sweden. E-mail: magnus.abrink{at}imbim.uu.se

Mast cells are implicated in rheumatoid arthritis, but the mechanism by which they contribute to disease progression is not clarified. Here we investigated whether mouse mast cell protease-4 (mMCP-4), a chymase present in the mast cell secretory granule, contributes to experimental arthritis. Two models of arthritis were investigated in mMCP-4^+/+ and mMCP-4^–/– DBA/1 mice: collagen-induced arthritis (CIA) was induced by immunization with collagen II (CII) in Freund’s complete adjuvant, and a passive model of arthritis was induced by administration of anti-CII antibodies. The clinical scores were significantly reduced in the mMCP-4^–/– animals as compared to mMCP-4^+/+ controls in both arthritis models. In CIA, the number of affected paws was lower in the CII-immunized mMCP-4^–/– mice, with less cartilage destruction, pannus formation, and mononuclear cell and mast cell influx in the mMCP-4^–/– joints. Interestingly, the lower clinical scores in the CII-immunized mMCP-4^–/– mice coincided with lower serum levels of immunoglobulin G anti-CII antibodies. Our findings identify a pathogenic role of mMCP-4 in autoimmune arthritis.—Magnusson, S. E., Pejler, G., Kleinau, S., Åbrink, M. Mast cell chymase contributes to the antibody response and the severity of autoimmune arthritis.

Key Words: protease and knockout mice • innate immune cell

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