title: Quantitative PPARγ expression affects the balance between tolerance and immunity.
abstract: 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 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 PPARγ 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 PPARγ in lymphocyte trafficking and cross talk between Th17 and B cells.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 70101, Taiwan.|Institute of Clinical Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 70101, Taiwan.|Institute of Clinical Medicine, National Cheng Kung University, Tainan 70101, Taiwan.|Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan.
authors.forename: Yau-Sheng
authors.initials: YS
authors.lastname: Tsai
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Nan-Shih
authors.initials: NS
authors.lastname: Liao
authors.affiliation: Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Ming-Shiou
authors.initials: MS
authors.lastname: Jan
authors.affiliation: National Laboratory Animal Center, National Applied Research Laboratories, Taipei 11529, Taiwan.
authors.forename: Chung-Tiang
authors.initials: CT
authors.lastname: Liang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Shih-Wen
authors.initials: SW
authors.lastname: Hsu
authors.affiliation: Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan.
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan.
authors.forename: Junne-Ming
authors.initials: JM
authors.lastname: Sung
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, North Carolina 27599, USA.
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 70101, Taiwan.|Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan.|Research Center of Infectious Disease and Signaling, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Pei-Jane
authors.initials: PJ
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D007108:Immune Tolerance; D007111:Immunity, Cellular; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D047495:PPAR gamma