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

ABSTRACT: PPAR-? 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-? 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-? 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-? 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.

SUBMITTER: Zhao W 

PROVIDER: S-EPMC4184099 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature