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.
| Original language | English |
|---|---|
| Article number | 8483 |
| Journal | Nature Communications |
| Volume | 6 |
| DOIs | |
| Publication status | Published - Sep 25 2015 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Chemistry(all)
- Physics and Astronomy(all)
Cite this
CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis. / Murayama, Masanori A.; Kakuta, Shigeru; Inoue, Asuka; Umeda, Naoto; Yonezawa, Tomo; Maruhashi, Takumi; Tateishi, Koichiro; Ishigame, Harumichi; Yabe, Rikio; Ikeda, Satoshi; Seno, Akimasa; Chi, Si Hua; Hashiguchi, Yuriko; Kurata, Riho; Tada, Takuya; Kubo, Sachiko; Sato, Nozomi; Liu, Yang; Hattori, Masahira; Saijo, Shinobu; Matsushita, Misao; Fujita, Teizo; Sumida, Takayuki; Iwakura, Yoichiro.
In: Nature Communications, Vol. 6, 8483, 25.09.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis
AU - Murayama, Masanori A.
AU - Kakuta, Shigeru
AU - Inoue, Asuka
AU - Umeda, Naoto
AU - Yonezawa, Tomo
AU - Maruhashi, Takumi
AU - Tateishi, Koichiro
AU - Ishigame, Harumichi
AU - Yabe, Rikio
AU - Ikeda, Satoshi
AU - Seno, Akimasa
AU - Chi, Si Hua
AU - Hashiguchi, Yuriko
AU - Kurata, Riho
AU - Tada, Takuya
AU - Kubo, Sachiko
AU - Sato, Nozomi
AU - Liu, Yang
AU - Hattori, Masahira
AU - Saijo, Shinobu
AU - Matsushita, Misao
AU - Fujita, Teizo
AU - Sumida, Takayuki
AU - Iwakura, Yoichiro
PY - 2015/9/25
Y1 - 2015/9/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84942627280&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942627280&partnerID=8YFLogxK
U2 - 10.1038/ncomms9483
DO - 10.1038/ncomms9483
M3 - Article
C2 - 26404464
AN - SCOPUS:84942627280
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 8483
ER -