Ciglitazone, a peroxisome proliferator-activated receptor gamma ligand, inhibits proliferation and differentiation of th17 cells.

Dong Hyeok Kim, Hyun-Ju Ihn, Chaerin Moon, Sang-Seok Oh, Soojong Park, Suk Kim, Keun Woo Lee, Kwang Dong Kim

Index: Biomol. Ther. (Seoul) 23(1) , 71-6, (2015)

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Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed PPARγ-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a PPARγ ligand, reduced both IL-1β-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-1β. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical PPARγ activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.