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However, its specific functions in the balance of immunity <jats:italic>in vivo<\/jats:italic> have been explored incompletely. In this study, by the age of 14 mo, <jats:italic>Pparg<\/jats:italic><jats:sup><jats:italic>C\/\u2212<\/jats:italic><\/jats:sup> mice with PPAR\u03b3 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<jats:sub>1<\/jats:sub>) expression and diminished migration toward S1P in the <jats:italic>Pparg<\/jats:italic><jats:sup><jats:italic>C\/<\/jats:italic>\u2212<\/jats:sup> splenocytes, which impeded lymphocyte egression. Mechanistically, increased Th17 polarization and IL-17 signaling in the <jats:italic>Pparg<\/jats:italic><jats:sup><jats:italic>C\/\u2212<\/jats:italic><\/jats:sup> CD4<jats:sup>+<\/jats:sup> T cells contributed to B-cell hyperactivation in the spleen. Finally, the activation of the remaining PPAR\u03b3 in <jats:italic>Pparg<\/jats:italic><jats:sup><jats:italic>C\/\u2212<\/jats:italic><\/jats:sup> mice by pioglitazone increased S1P<jats:sub>1<\/jats:sub> levels, reduced the Th17 population in the spleen and ameliorated splenomegaly. Taken together, our data demonstrated that reduction of <jats:italic>Pparg<\/jats:italic> expression in T-helper cells is critical for spontaneous SLE-like autoimmune disease development; we also revealed a novel function of PPAR\u03b3 in lymphocyte trafficking and cross talk between Th17 and B cells.<\/jats:p>","DOI":"10.1038\/srep26646","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T09:24:29Z","timestamp":1464168269000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Quantitative PPAR\u03b3 expression affects the balance between tolerance and immunity"],"prefix":"10.1038","volume":"6","author":[{"given":"Ya-Hui","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yau-Sheng","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Chieh","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan-Shih","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Shiou","family":"Jan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung-Tiang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Wen","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Chung","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junne-Ming","family":"Sung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyo","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Jane","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,5,25]]},"reference":[{"key":"BFsrep26646_CR1","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.autrev.2011.02.006","volume":"10","author":"J Sellner","year":"2011","unstructured":"Sellner, J. et al. 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