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Quantitative PPAR? expression affects the balance between tolerance and immunity.

ABSTRACT: PPAR? 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, Pparg(C/-) mice with PPAR? 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 (S1P1) expression and diminished migration toward S1P in the Pparg(C/-) splenocytes, which impeded lymphocyte egression. Mechanistically, increased Th17 polarization and IL-17 signaling in the Pparg(C/-) CD4(+) T cells contributed to B-cell hyperactivation in the spleen. Finally, the activation of the remaining PPAR? in Pparg(C/-) mice by pioglitazone increased S1P1 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 PPAR? in lymphocyte trafficking and cross talk between Th17 and B cells.

SUBMITTER: Liu YH

PROVIDER: S-EPMC4879582 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Quantitative PPARγ expression affects the balance between tolerance and immunity.

Liu Ya-Hui YH Tsai Yau-Sheng YS Lin Shih-Chieh SC Liao Nan-Shih NS Jan Ming-Shiou MS Liang Chung-Tiang CT Hsu Shih-Wen SW Chen Wen-Chung WC Sung Junne-Ming JM Maeda Nobuyo N Tsai Pei-Jane PJ

Scientific reports 20160525

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, Pparg(C/-) 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 associ ...[more]

PMID: 27221351

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Quantitative PPAR? expression affects the balance between tolerance and immunity.

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Quantitative PPARγ expression affects the balance between tolerance and immunity.

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