Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily whose ligands are liophilic compounds. Early studies on PPARs action revealed their role in diverse aspects in development and homeostasis. Despite the substantial research effort targeting PPARs role in metabolism including lipid metabolism, glucose homeostasis and adipogenesis the exact mechanisms by which PPARs regulate metabolic processes are poorly understood. Yet another facet of PPARs action is that there is an accumulating body of evidence showing that these transcription factors are active in immune cells and participate in the regulation of immune response. Therefore, PPARs represent a unique class of transcription factors that links metabolism to immunoregulation. In spite of the in vitro evidence implicating PPARγ in immunoregulation, in vivo studies on the role of PPARγ in immune response have been lacking. It is also poorly understood how the transcription events in metabolism connect to the transcriptional regulation of cell differentation and immunoregulation. Current proposal aims to deliver two objectives. The in vivo role of PPARgamma in immunoregulation will be investigated in infection studies in which mouse strains with macrophage and dendritic cell specific conditional PPARγ deletion will be infected with pathogens that trigger TH1 or TH2 type immune responses. Our second objective is to understand better the mechanism of regulatory events directed by PPARγ. We will test our hypothesis that a section of PPARγ signalling in the regulation of inflammation occurs via the action of microRNAs. The successful completion of our proposal will define the in vivo importance of PPARγ in immunoregulation and potentially unveil another layer in the mode of actions of PPARγ