Quantitative PPARγ expression affects the balance between tolerance and immunity

Ya Hui Liu, Yau Sheng Tsai, Shih Chieh Lin, Nan Shih Liao, Ming Shiou Jan, Chung Tiang Liang, Shih Wen Hsu, Wen Chung Chen, Junne Ming Sung, Nobuyo Maeda, Pei Jane Tsai

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18 引文 斯高帕斯(Scopus)

摘要

PPARγ modulates energy metabolism and inflammation. However, its specific functions in the balance of immunity in vivo have been explored incompletely. In this study, by the age of 14 mo, PpargC/- mice with PPARγ expression at 25% of the normal level exhibited high autoantibody levels and developed mesangial proliferative glomerulonephritis, which resembled systemic lupus erythematosus (SLE)-like autoimmune disease. These symptoms were preceded by splenomegaly at an early age, which was associated with increases in splenocyte accumulation and B-cell activation but not with relocation of hematopoiesis to the spleen. The mechanism of splenic lymphocyte accumulation involved reduced sphingosine-1-phosphate receptor 1 (S1P 1) expression and diminished migration toward S1P in the PpargC/- splenocytes, which impeded lymphocyte egression. Mechanistically, increased Th17 polarization and IL-17 signaling in the PpargC/- CD4+ T cells contributed to B-cell hyperactivation in the spleen. Finally, the activation of the remaining PPARγ in PpargC/- mice by pioglitazone increased S1P 1 levels, reduced the Th17 population in the spleen, and ameliorated splenomegaly. Taken together, our data demonstrated that reduction of Pparg expression in T-helper cells is critical for spontaneous SLE-like autoimmune disease development; we also revealed a novel function of PPARγ in lymphocyte trafficking and cross talk between Th17 and B cells.

原文English
文章編號26646
期刊Scientific reports
6
DOIs
出版狀態Published - 2016 5月 25

All Science Journal Classification (ASJC) codes

  • 多學科

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