title: The peroxisome-proliferator activated receptor-γ agonist pioglitazone modulates aberrant T cell responses in systemic lupus erythematosus.
abstract: PPAR-γ agonists can suppress autoimmune responses and renal inflammation in murine lupus but the mechanisms implicated in this process remain unclear. We tested the effect of the PPAR-γ agonist pioglitazone in human lupus and control PBMCs with regard to gene regulation and various functional assays. By Affymetrix microarray analysis, several T cell-related pathways were significantly highlighted in pathway analysis in lupus PBMCs. Transcriptional network analysis showed IFN-γ as an important regulatory node, with pioglitazone treatment inducing transcriptional repression of various genes implicated in T cell responses. Confirmation of these suppressive effects was observed specifically in purified CD4+ T cells. Pioglitazone downregulated lupus CD4+ T cell effector proliferation and activation, while it significantly increased proliferation and function of lupus T regulatory cells. We conclude that PPAR-γ agonists selectively modulate CD4+ T cell function in SLE supporting the concept that pioglitazone and related,-agents should be explored as potential therapies in this disease.
authors: Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors: Wenpu
authors: W
authors: Zhao
authors: Celine C
authors: CC
authors: Berthier
authors: Emily E
authors: EE
authors: Lewis
authors: W Joseph
authors: WJ
authors: McCune
authors: Matthias
authors: M
authors: Kretzler
authors: Mariana J
authors: MJ
authors: Kaplan
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D007074:Immunoglobulin G; D047495:PPAR gamma; D045162:Thiazolidinediones; D004247:DNA; D000077205:Pioglitazone
keywords: Gene expression; Systemic lupus erythematosus;; T cells;
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