The effect of synthetic retinoid, Am80, on T helper cell development and antibody production in murine collagen-induced arthritis.
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)-gamma 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-gamma 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.
Sato
Aya
A
Department of Medicine and Rheumatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Watanabe
Kaori
K
Kaneko
Kayoko
K
Murakami
Yousuke
Y
Ishido
Miwako
M
Miyasaka
Nobuyuki
N
Nanki
Toshihiro
T
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology*; D001565:Benzoates / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007596:Joints / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012176:Retinoids / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D012720:Severity of Illness Index; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D013764:Tetrahydronaphthalenes / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use
D001565:Benzoates; D012176:Retinoids; D013764:Tetrahydronaphthalenes; C061133:tamibarotene