title: Local delivery of T-bet shRNA reduces inflammation in collagen II-induced arthritis via downregulation of IFN-γ and IL-17.
abstract: Th1 and Th17 cells are involved in the pathogenesis of rheumatoid arthritis (RA). T-bet, a Th1-specific transcription factor, appears to drive the maturation of Th1 and IFN-γ secretion. In the present study, we established the T-bet shRNA recombinant plasmid (p-T-shRNA) and explored its possible anti-inflammatory effect in a collagen-induced arthritis (CIA) model by local injection of plasmid vectors. For the initiation of CIA, DBA/1J mice were immunized with type II collagen (CII) in Freund's adjuvant and the CII-immunized mice were treated with p-T-shRNA. Levels of T-bet, IFN-γ, IL-17 and RORγt mRNA in splenocytes and synovial joints were measured by quantitative real-time PCR and T-bet expression in joint tissue was detected by immunohistochemistry staining. The intracellular IFN-γ and IL-17 were analyzed by flow cytometry (FCM). The results demonstrated that therapeutic administration on the local joints with p-T-shRNA signiﬁcantly suppressed IFN-γ and IL-17 gene expression and improved the pathogenesis of arthritis in CIA mice, while administration of a plasmid expressing T-bet (pIRES-T-bet) accelerated the disease onset. Our study suggests that T-bet may be developed as a potential target for arthritis therapy.
authors.affiliation: Department of Immunology, Institute of Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xue
authors.affiliation: The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Immunology, Institute of Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Immunology, Institute of Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Prince Amoatt
authors.initials: PA
authors.lastname: Barnie
authors.affiliation: Department of Immunology, Institute of Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Immunology, Institute of Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Institute of Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Immunology, Institute of Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Immunology, Institute of Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D024043:Collagen Type II; D015536:Down-Regulation; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism; D007596:Joints / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D024043:Collagen Type II; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D034741:RNA, Small Interfering; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma