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

Masanori A. Murayama, Shigeru Kakuta, Asuka Inoue, Naoto Umeda, Tomo Yonezawa, Takumi Maruhashi, Koichiro Tateishi, Harumichi Ishigame, Rikio Yabe, Satoshi Ikeda, Akimasa Seno, Si Hua Chi, Yuriko Hashiguchi, Riho Kurata, Takuya Tada, Sachiko Kubo, Nozomi Sato, Yang Liu, Masahira Hattori, Shinobu SaijoMisao Matsushita, Teizo Fujita, Takayuki Sumida, Yoichiro Iwakura

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 languageEnglish
Article number8483
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 2015 Sep 25
Externally publishedYes

Fingerprint

arthritis
regulators
complement
Arthritis
mice
Refractory materials
Rheumatoid Arthritis
Genes
Chemical activation
Arthus Reaction
Alternative Complement Pathway
Intra-Articular Injections
Autoimmune Experimental Encephalomyelitis
Complement Activation
Transgenic Mice
embryos
infectious diseases
refractories
Proteins
Embryonic Structures

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Murayama, M. A., Kakuta, S., Inoue, A., Umeda, N., Yonezawa, T., Maruhashi, T., ... Iwakura, Y. (2015). CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis. Nature Communications, 6, [8483]. https://doi.org/10.1038/ncomms9483

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 journalArticle

Murayama, MA, Kakuta, S, Inoue, A, Umeda, N, Yonezawa, T, Maruhashi, T, Tateishi, K, Ishigame, H, Yabe, R, Ikeda, S, Seno, A, Chi, SH, Hashiguchi, Y, Kurata, R, Tada, T, Kubo, S, Sato, N, Liu, Y, Hattori, M, Saijo, S, Matsushita, M, Fujita, T, Sumida, T & Iwakura, Y 2015, 'CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis', Nature Communications, vol. 6, 8483. https://doi.org/10.1038/ncomms9483
Murayama MA, Kakuta S, Inoue A, Umeda N, Yonezawa T, Maruhashi T et al. CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis. Nature Communications. 2015 Sep 25;6. 8483. https://doi.org/10.1038/ncomms9483
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. / CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis. In: Nature Communications. 2015 ; Vol. 6.
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