Local delivery of T-bet shRNA reduces inflammation in collagen II‑induced arthritis via downregulation of IFN-γ and IL-17

Xue,Yuan; Yang,Yong; Su,Zhaoliang; Barnie,Prince Amoatt; Zheng,Dong; Zhang,Yun; Xu,Yan; Wang,Shengjun; Xu,Huaxi

doi:10.3892/mmr.2014.1893

Local delivery of T-bet shRNA reduces inflammation in collagen II‑induced arthritis via downregulation of IFN-γ and IL-17

Authors:
- Yuan Xue
- Yong Yang
- Zhaoliang Su
- Prince Amoatt Barnie
- Dong Zheng
- Yun Zhang
- Yan Xu
- Shengjun Wang
- Huaxi Xu
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Affiliations: Department of Immunology, Institute of Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
Published online on: January 13, 2014 https://doi.org/10.3892/mmr.2014.1893
Pages: 899-903

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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.

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