@article{e9030f57418e4fda88943b853b581fa0,
title = "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(H 2 O) 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.",
author = "Murayama, {Masanori A.} and Shigeru Kakuta and Asuka Inoue and Naoto Umeda and Tomo Yonezawa and Takumi Maruhashi and Koichiro Tateishi and Harumichi Ishigame and Rikio Yabe and Satoshi Ikeda and Akimasa Seno and Chi, {Si Hua} and Yuriko Hashiguchi and Riho Kurata and Takuya Tada and Sachiko Kubo and Nozomi Sato and Yang Liu and Masahira Hattori and Shinobu Saijo and Misao Matsushita and Teizo Fujita and Takayuki Sumida and Yoichiro Iwakura",
note = "Funding Information: We thank Dr Yuko Kimura and Dr Wen-Chao Song for assistance with the complement activation assay and Dr Junichi Miyazaki for the pCXN2 vector. We thank Dr Masato Nose for his excellent histological analysis of arthritis and thoughtful discussion. We thank Dr Shuhei Ogawa for an installation of C3−/− mice, and all the members of our laboratory for kind cooperation, discussion and animal care. This work was supported by CREST of the Japan Science and Technology Agency (to Y.I.), the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry (to Y.I.), Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (to Y.I.) and M.A.M. is a research assistant of the of the CREST program. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",
year = "2015",
month = sep,
day = "25",
doi = "10.1038/ncomms9483",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}