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THU0502 Ad Promotes the Differentiation of TH17 Cell and Exacerbates Disease Progression in CIA Model via Enhancing TH17 Response
  1. M. Zhang
  1. Rheumatology Department, The First Affiliated Hospital of Nanjing Medical University Jiangsu Province hospital, Nanjing, Jiangsu province, China

Abstract

Background Adiponectin (AD), produced prevalently by adipose tissues, has suggested playing a significant role in chronic inflammation and immune response. The relation between AD and rheumatoid arthritis (RA) has been a topic of much interest recently. We previously reported the high expression of AD in the inflammated joint of RA. Recent studies indicated that circulating adiponectin levels are associated with progressive of radiographic joint destruction in RA, suggesting that AD is involved in bone erosion in RA, but the mechanism remained unclear. We hypothesize that local AD might directly involved in the progression of synovial inflammation and joint destruction in RA by enhancing Th17 cell response. In this study, we will investigate a role of AD on promoting the differentiation of naïve T cell to Th17 cell and bone erosion in collagen-induced arthritis (CIA) mice.

Objectives To investigate a role of Adiponectin (AD) on promoting the differentiation of naïve T cell to Th17 cell and bone erosion in collagen-induced arthritis (CIA) mice.

Methods Purified naïve T cells were cultured in anti-CD3 mAb and anti-CD28 mAb precoated with TGF-β, IL-6, IL-23 in the presence and absence of AD (0.1, 1 or 10 μg/ml). After 72 hours of culture, the frequencies of Th17 cells were measured by flow cytometry; the expression of IL-17, ROR-γt, IL-21, IL-22 and IL-23 were determined by real-time PCR and ELISA. Intraarticularly injected of AD 10 μl (1 μg/1 μl) into the knee joint of CIA mice was to analysis the role of AD on CIA development, Th17 cell expression.

Results The frequencies of Th17 cells were significantly increased with the treatment of AD 10 μg/ml. The expression of IL-17, ROR-γt and IL-23 mRNA were significantly increased upon AD 10 μg/ml stimulation. Consistently with mRNA expression, IL-17 levels were significantly elevated in culture supernatants with 10 μg/ml AD treatments. Intraarticular injection of AD into the knee joint of CIA mice aggravated arthritic development and bone erosion, triggered higher expression of IL-17, IL-22, IL-23 mRNA in CIA model.

Conclusions These findings identify a role of AD on enhancing the differentiation of Th17 cell and exacerbating disease progression in CIA model via enhancing Th17 response.

References

  1. Jun Deng, Yang Liu, Min Yang. etal. Leptin exacerbates collagen-induced arthritis via enhancing Th17 cell response. 2012.

  2. Tan W, Wang F, Zhang M, etal. High adiponectin and adiponectin receptor 1 expression in synovial fluids and synovial tissues of patients with rheumatoid arthritis. Semin Arthritis Rheum. 2009;38(6):420-7.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.4176

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