title: Schistosoma japonicum cystatin attenuates murine collagen-induced arthritis.
abstract: Recombinant SjCystatin (rSjCystatin), a recombinant protein of Schistosoma japonicum cystatin, has been reported to have an effect on immunoregulation mediated by IL-10 induction. Rheumatoid arthritis (RA) is a common autoimmune inflammatory arthropathy, and recombinant immune-modulating drugs for RA treatment are under development. We aimed to study the putative immune regulation of rSjCystatin and its prophylactic/therapeutic effects on murine collagen-induced arthritis (CIA). CIA was induced in DBA/1 mice by inoculation with bovine collagen II (CII). rSjCystatin was administered prior or post development of CIA. The severity of CIA was assessed using established clinical and histopathological scoring systems. The incidence was also determined. The CII-specific antibodies in sera and cytokines in splenocyte culture supernatants were measured by ELISA. Th1/Th2/Th17 cells and Tregs development in splenocytes were monitored by flow cytometry. The inflammatory mediators in the diseased joint were semiquantitated by qPCR. Prophylactic injection of rSjCystatin attenuated paw clinical scores, incidence, and histopathology scores of joints in CIA mice. The arthritis-alleviative effects were closely associated with the augmentation of IL-4, IL-10, and collagen-specific IgG1, and with the distinct reduction of IFN-γ, collagen-specific IgG2a, and the marked decrease of proinflammatory cytokines IL-6, IL-17, and TNF-α and RANKL. The data indicate that rSjCystatin may prevent cartilage destruction and inflammation of joints in CIA mice. The effects are related to the inhibitory modulation of Th1 and Th17 and upregulation of Tregs and Th2 via a shift of cytokines profiling from Th1 to Th2 response.
authors.affiliation: Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, 230022, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, 230022, China.|Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, 230022, China.
authors.forename: Faustina
authors.initials: F
authors.lastname: Pappoe
authors.affiliation: Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, 230022, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, 230022, China.|Department of Blood Transfusion, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Wen
authors.affiliation: Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, 230022, China.
authors.forename: Qingli
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, 230022, China.
authors.forename: Shushu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Laboratory Diagnosis, the Provincial Tumor Hospital of Anhui Medical University, Hefei, 230022, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Deng
authors.affiliation: Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, 230022, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, 230022, China. xyhong1964@163.com.|Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. xyhong1964@163.com.|Department of Pathogen Biology, Anhui Medical University, Hefei, 230022, China. xyhong1964@163.com.|Department of Clinical Laboratory Medicine, Anhui Medical University, Hefei, 230022, China. xyhong1964@163.com.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, 230022, China. shenjilong53@126.com.|Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. shenjilong53@126.com.|Department of Pathogen Biology, Anhui Medical University, Hefei, 230022, China. shenjilong53@126.com.|Department of Clinical Laboratory Medicine, Anhui Medical University, Hefei, 230022, China. shenjilong53@126.com.
authors.forename: Jilong
authors.initials: J
authors.lastname: Shen
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D024043:Collagen Type II / Q000009:adverse effects* / Q000276:immunology; D015891:Cystatins / Q000008:administration & dosage* / Q000276:immunology; D015801:Helminth Proteins / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012549:Schistosoma japonicum / Q000737:chemistry / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D024043:Collagen Type II; D015891:Cystatins; D015801:Helminth Proteins; D020381:Interleukin-17; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4
keywords: Collagen-induced arthritis; Cystatin; Immune modulation; Schistosoma japonicum