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Your search keyword '"Ishigame H"' showing total 2 results
Start Over Author "Ishigame H" Publisher nature pub. group
2 results on '"Ishigame H"'

1. CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis.

Author

Murayama MA, Kakuta S, Inoue A, Umeda N, Yonezawa T, Maruhashi T, Tateishi K, Ishigame H, Yabe R, Ikeda S, Seno A, Chi HH, Hashiguchi Y, Kurata R, Tada T, Kubo S, Sato N, Liu Y, Hattori M, Saijo S, Matsushita M, Fujita T, Sumida T, and Iwakura Y

Subjects
Adipokines genetics, Adult, Animals, Arthritis, Experimental genetics, Arthritis, Experimental pathology, Arthritis, Rheumatoid genetics, Arthritis, Rheumatoid pathology, Arthus Reaction genetics, Arthus Reaction immunology, Arthus Reaction metabolism, Blotting, Western, Collagen immunology, Collagen metabolism, Complement C3-C5 Convertases immunology, Complement C3a immunology, Complement C5a immunology, Complement Pathway, Alternative genetics, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental genetics, Encephalomyelitis, Autoimmune, Experimental immunology, Encephalomyelitis, Autoimmune, Experimental metabolism, Female, Flow Cytometry, Humans, Immunoprecipitation, Macrophages immunology, Male, Mice, Mice, Knockout, Mice, Transgenic, Middle Aged, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Synovial Membrane cytology, Synovial Membrane metabolism, Adipokines immunology, Arthritis, Experimental immunology, Arthritis, Rheumatoid immunology, Complement Pathway, Alternative immunology
Abstract

The complement system is important for the host defence against infection as well as for the development of inflammatory diseases. Here we show that C1q/TNF-related protein 6 (CTRP6; gene symbol C1qtnf6) expression is elevated in mouse rheumatoid arthritis (RA) models. C1qtnf6(-/-) mice are highly susceptible to induced arthritis due to enhanced complement activation, whereas C1qtnf6-transgenic mice are refractory. The Arthus reaction and the development of experimental autoimmune encephalomyelitis are also enhanced in C1qtnf6(-/-) mice and C1qtnf6(-/-) embryos are semi-lethal. We find that CTRP6 specifically suppresses the alternative pathway of the complement system by competing with factor B for C3(H2O) binding. Furthermore, treatment of arthritis-induced mice with intra-articular injection of recombinant human CTRP6 cures the arthritis. CTRP6 is expressed in human synoviocytes, and CTRP6 levels are increased in RA patients. These results indicate that CTRP6 is an endogenous complement regulator and could be used for the treatment of complement-mediated diseases.

Published
2015
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2. IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2(+)Vγ6(+)γδ T cells.

Author

Akitsu A, Ishigame H, Kakuta S, Chung SH, Ikeda S, Shimizu K, Kubo S, Liu Y, Umemura M, Matsuzaki G, Yoshikai Y, Saijo S, and Iwakura Y

Subjects
Animals, Arthritis metabolism, Chemokine CCL2 genetics, Chemokine CCL2 metabolism, Gene Expression Regulation immunology, Interleukin 1 Receptor Antagonist Protein genetics, Interleukin-17 genetics, Joints metabolism, Joints pathology, Mice, Mice, Knockout, Receptors, Antigen, T-Cell, gamma-delta, Receptors, Interleukin-1 Type I genetics, Receptors, Interleukin-1 Type I metabolism, T-Lymphocyte Subsets immunology, Arthritis immunology, Autoimmune Diseases metabolism, Interleukin 1 Receptor Antagonist Protein metabolism, Interleukin-17 metabolism, Lymphocyte Activation physiology, T-Lymphocyte Subsets physiology
Abstract

Interleukin-17 (IL-17)-producing γδ T (γδ17) cells have been implicated in inflammatory diseases, but the underlying pathogenic mechanisms remain unclear. Here, we show that both CD4(+) and γδ17 cells are required for the development of autoimmune arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Specifically, activated CD4(+) T cells direct γδ T-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17 reporter mice reveal that the Vγ6(+) subset of CCR2(+) γδ T cells preferentially produces IL-17 in inflamed joints. Importantly, because IL-1Ra normally suppresses IL-1R expression on γδ T cells, IL-1Ra-deficient mice exhibit elevated IL-1R expression on Vγ6(+) cells, which play a critical role in inducing them to produce IL-17. Our findings demonstrate a pathogenic mechanism in which adaptive and innate immunity induce an autoimmune disease in a coordinated manner.

Published
2015
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