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

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.

• Authors: Masanori A Murayama, Shigeru Kakuta, Asuka Inoue, Naoto Umeda, Tomo Yonezawa, Takumi Maruhashi, Koichiro Tateishi, Harumichi Ishigame, Rikio Yabe, Satoshi Ikeda, Akimasa Seno, Hsi-Hua Chi, Yuriko Hashiguchi, Riho Kurata, Takuya Tada, Sachiko Kubo, Nozomi Sato, Yang Liu, Masahira Hattori, Shinobu Saijo, Misao Matsushita, Teizo Fujita, Takayuki Sumida, Yoichiro Iwakura
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 8483 (Sep 25 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 26404464 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adipokines
• C1qTNF6 protein, human
• CTRP6 protein, mouse
• Complement C3a
• Complement C5a
• Collagen
• Complement C3-C5 Convertases

Topics

• Adipokines (genetics, immunology)
• Adult
• Animals
• Arthritis, Experimental (genetics, immunology, pathology)
• Arthritis, Rheumatoid (genetics, immunology, pathology)
• Arthus Reaction (genetics, immunology, metabolism)
• Blotting, Western
• Collagen (immunology, metabolism)
• Complement C3-C5 Convertases (immunology)
• Complement C3a (immunology)
• Complement C5a (immunology)
• Complement Pathway, Alternative (genetics, immunology)
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (genetics, immunology, 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, metabolism)