Therapeutic Effect of Rosiglitazone-Mediated Dendritic Cells in Established Arthritis in Mice

Jin Jung Choi¹, Sang-Yoon Jung², Kyung-Su Park³, Chong-Hyeon Yoon⁴ and Dae-Seog Lim⁵, ¹Rheumatology, CHA University Medical Center at Bundang, Sungnam, Korea, Republic of (South), ²Internal Medicine, Bundang CHA Medical Center, Seongnam, Korea, Republic of (South), ³Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea, Republic of (South), ⁴Rheumatology, The Catholic University of Korea, Uijeongbu St. Mary's Hospital, Uijeongbu, Korea, Republic of (South), ⁵Department of biotechnology, CHA University, Sungnam, Korea, Republic of (South)

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Animal models, dendritic cells and rheumatoid arthritis, PPAR-gamma, T-Regulatory Cells

Session Information

Date: Sunday, November 5, 2017

Title: Rheumatoid Arthritis – Animal Models Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Rosiglitazone is a selective ligand for peroxisome proliferator-activated receptor-gamma (PPAR-γ), which is expressed by antigen presenting cells (APCs) and plays a fundamental role in immune responses. Tolerogenic dendritic cells (tDCs) are professional APCs with antigen-specific immune regulation to induce autoimmune tolerance, suggesting the potential as antigen-specific immunotherapy for autoimmune diseases. The aim of this study was to investigate therapeutic effects of rosiglitazone-mediated DC (Rosi-DC) in a collagen-induced arthritis (CIA) mouse model.

Methods:

Rosi-DCs were generated by treating immature DCs with TNF-α, type II collagen, and rosiglitazone. CIA mice then received subcutaneously two injections of Rosi-DCs. The severity of arthritis was then assessed three times until Day 50 post-primary immunization. The phenotypes of the DC and regulatory T (Treg) cell populations in CIA mice were determined by flow cytometry and the effect of Rosi-DCs on the secretion of autoimmunity-inducing cytokines was examined by ELISA.

Results:

Rosi-DCs expressed lower levels of DC-related surface markers (CD80, CD86, CD40 and CD54) than mature DCs. Rosi-DCs produced lower levels of pro-inflammatory cytokines (IL-1β, IL-6, and IL-12p70) than mDCs. Upon the co-culture of DCs and T lymphocytes, Rosi-DCs markedly increased FoxP3+CD4+CD25+ Treg cell population and reduced the Th1/Th17 cell population.

Histopathological examination revealed that the degree of inflammation in the paws of Rosi-DC-treated mice was much lower than that in the paws of PBS-treated CIA mice. In vivo, the percentage of Treg cells in the spleens and inguinal lymph nodes of mice vaccinated with type II collagen-pulsed Rosi-DCs was markedly higher than that in mice injected with Ag-mismatched (myosin pulsed) or Ag-unpulsed Rosi-DCs and PBS-treated CIA mice. Treatment with type II collagen-pulsed Rosi-DCs resulted in a reduction in the percentage of Th1 and Th17 cells within the splenocyte population.

Conclusion:

In this study, these results clearly show that rosiglitazone-mediated DCs ameliorate CIA, most likely via the induction of antigen-specific Treg cells.

Disclosure: J. J. Choi, None; S. Y. Jung, None; K. S. Park, None; C. H. Yoon, None; D. S. Lim, None.

To cite this abstract in AMA style:

Choi JJ, Jung SY, Park KS, Yoon CH, Lim DS. Therapeutic Effect of Rosiglitazone-Mediated Dendritic Cells in Established Arthritis in Mice [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/therapeutic-effect-of-rosiglitazone-mediated-dendritic-cells-in-established-arthritis-in-mice/. Accessed .

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