title: Electroacupuncture attenuates collagen-induced arthritis in rats through vasoactive intestinal peptide signalling-dependent re-establishment of the regulatory T cell/T-helper 17 cell balance.
abstract: OBJECTIVE
  Imbalance between T-helper 17 (Th17) cells and regulatory T (Treg) cells is causally linked to the development of rheumatoid arthritis (RA). In this study, we tested the hypothesis that electroacupuncture (EA) confers therapeutic benefits in RA through activation of vasoactive intestinal peptide (VIP)-dependent signalling and restoration of the Th17/Treg cell balance.
  
  
  METHODS
  A collagen-induced arthritis (CIA) model was induced in Sprague-Dawley rats by injection of bovine type II collagen in incomplete Freund's adjuvant on day 0 and day 7. Three days after the second injection, EA was given at acupuncture points GB39 and ST36 three times per week for 4 weeks. To block VIP signalling, [D-P-Cl-Phe(6)-Leu(17)]-VIP, a VIP receptor antagonist, was administered intraperitoneally 30 min before EA. Inflammatory and pathological responses in the joint were assessed. Synovial VIP receptor mRNA levels and Treg and Th17 cell frequencies in the spleen were determined.
  
  
  RESULTS
  EA significantly reduced the severity of CIA, as evidenced by reduced paw volumes, arthritis scores and inflammation scores. EA significantly increased mRNA expression of the VIP receptor VPAC1 and led to an elevation in CD4(+)FOXP3(+) Treg cell frequency and a reduction in CD4(+)IL17(+) Th17 cell frequency. Pre-injection of a VIP receptor antagonist significantly reversed EA-induced expansion of Treg cells, but did not alter the frequencies of Th17 cells.
  
  
  CONCLUSIONS
  EA exerts anti-inflammatory effects in a collagen-induced rat model of arthritis. These effects appear to be mediated through activation of VIP signalling and re-establishment of the Th17/Treg cell balance.
authors.affiliation: Laboratory Center of Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Laboratory Center of Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Department of Acupuncture and Moxibustion, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Lian-Bo
authors.initials: LB
authors.lastname: Li
authors.affiliation: Institute of Integrative Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Xin-Tong
authors.initials: XT
authors.lastname: Yu
authors.affiliation: Laboratory Center of Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Laboratory Center of Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Wen-Jia
authors.initials: WJ
authors.lastname: Yang
authors.affiliation: Laboratory Center of Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Laboratory Center of Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Laboratory Center of Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Pathology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: Laboratory Center of Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China Institute of Acupuncture-Moxibustion and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Chen
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D003094:Collagen / Q000009:adverse effects / Q000276:immunology; D015671:Electroacupuncture; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014660:Vasoactive Intestinal Peptide / Q000276:immunology*
chemical_list: D014660:Vasoactive Intestinal Peptide; D003094:Collagen