The peroxisome-proliferator activated receptor-γ agonist pioglitazone modulates aberrant T cell responses in systemic lupus erythematosus.

Publication Type:

Journal Article

Source:

Clin Immunol, Volume 149, Issue 1, p.119-32 (2013)

Keywords:

asb, Cell Proliferation, Cells, Cultured, DNA, Gene Expression Profiling, Gene Expression Regulation, Humans, Hypoglycemic Agents, Immunoglobulin G, Leukocytes, Mononuclear, Lupus Erythematosus, Systemic, Oligonucleotide Array Sequence Analysis, PPAR gamma, T-Lymphocyte Subsets, T-Lymphocytes, Thiazolidinediones

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.