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Nat Commun. 2015 Sep 25;6:8483. doi: 10.1038/ncomms9483.

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

Author information

1
Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan.
2
Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo 108-8639, Japan.
3
Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-0882, Japan.
4
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama 332-0012, Japan.
5
Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
6
Department of Systems Biomedicine, National Research Institute of Child Health and Development, Tokyo 157-8535, Japan.
7
Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
8
Department of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan.
9
Fukushima Prefectural General Hygiene Institute, Fukushima 960-8142, Japan.

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.

PMID:
26404464
PMCID:
PMC4598845
DOI:
10.1038/ncomms9483
[Indexed for MEDLINE]
Free PMC Article

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