Vol.20 No.3

Original Article

The effect of synthetic retinoid, Am80, on T helper cell development and antibody production in murine collagen-induced arthritis

Authors

Aya Sato1 , Kaori Watanabe1 , Kayoko Kaneko1 , Yousuke Murakami1 , Miwako Ishido1 , Nobuyuki Miyasaka1,2 , Toshihiro Nanki1,3

  • Department of Medicine and Rheumatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
  • Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo 113-8519, Japan
  • Department of Pharmacovigilance, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Received:

12 November 2009

Accepted:

30 November 2009

Published online:

29 December 2009

Full Text

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Abstract

Retinoids are known to promote T helper (Th)2 and regulatory T cell (Treg) differentiation, and suppress Th1 and Th17 in vitro. Am80, a synthetic retinoid, is reported to ameliorate collagen-induced arthritis (CIA). The aims of this study are to determine the effects of Am80 on CIA in detail, and on Th development and antibody (Ab) production in vivo. Murine CIA was induced by immunization with bovine type II collagen (CII) at days 1 and 22. Treatment with Am80 from day 1 to 35 significantly lowered clinical arthritis score, suppressed cellular infiltration and bone destruction in the joint, decreased interleukin (IL)-17 and increased interferon (IFN)-γ production by CII-stimulated splenocytes, and decreased proportion of Foxp3+ splenic CD4 T cells and serum anti-CII Ab levels. Thus, Am80 inhibited Th17 and Treg and enhanced Th1 differentiation in vivo. In contrast, Am80 applied from day 15 to 35 did not alter arthritis score, IL-17 or IFN-γ production by CII-stimulated splenocytes, but decreased the proportion of Foxp3+ splenic CD4 T cells and serum anti-CII Ab levels. Am80 exhibits inhibitory effects on CIA and might regulate both Th development and Ab production in vivo. Decreased Th17 by treatment with Am80 might be responsible for the attenuation of arthritis.

Key words

Am80 - Retinoid - Th17 - Th1 - Collagen-induced arthritis