Roles of the PPAR/RXR nuclear hormone receptors in dendritic cells differentiation and function

Roles of the PPAR/RXR nuclear hormone receptors in dendritic cells differentiation and function

Dendritic cells (DC) are the most efficient professional antigen presenting cells. They play a major role in the initiation of T cell mediated immunity and are considered promising targets for immunotherapy. The primary function of dendritic cells is to capture and process antigen (immature DC), then to present the processed antigen and activate specific T cells (mature DC). The differentiation of dendritic cells is a very complicated process, the specific genes whose expression mediate differentiation of progenitor cells to DC are largely undefined.

Our research focuses on the molecular and cell biology of lipid activated transcription factors so called PPAR receptors. The peroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors which belong to the nuclear hormone receptor family. There are three subtypes of PPARs, which are characterized by distinct tissue distribution patterns: PPARalfa, gamma and delta. PPARgamma function as regulators of lipid and glucose metabolism and adypocyte differentiation. Along with its expression in adypocyte tissue, PPARgamma has also been shown to be expressed in myeloid cells. A recent DNA CHIP study has shown that PPARgamma and some of its target genes expression dramatically increased in the immature form of dendritic cells compare with monocytes. These data prompted us to investigate the role of PPARgamma on the differentiation of myeloid type of DC. Our goal is defining the role of PPARgamma signaling pathways in dendritic cells. We would like to compare the gene expression profile of monocyte and dendritic cells using DNA microarray technology and quantitative PCR.