BioProject

Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserve self-tolerance and prevent chronic inflammation and autoimmune pathologies. More...

Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserve self-tolerance and prevent chronic inflammation and autoimmune pathologies. However the diverse array of phagocytes residing within different tissues combined with the necessarily prompt nature of apoptotic cell clearance has made it difficult to study this process in situ. Thus, the full spectrum of functions executed by tissue resident phagocytes in response to homeostatic apoptosis remains unclear. We used microarrays to characterize the transcriptome within murine intestinal dendritic cells and macrophages both before and after in situ phagocytosis of apoptotic intestinal epithelial cells. Overall design: We generated transgenic mice (VDTR) where the primate diphtheria toxin receptor (DTR) fused to enhanced green fluorescent protein (GFP) was driven by the villin promoter enabling expression in intestinal epithelial cells (IEC) of the small and large intestine. We reasoned that intraperitoneal injection of diphtheria toxin would induce apoptosis specifically in IEC, whose sampling could be monitored by tracking the appearance of GFP within professional phagocytes. We chose to explore the transcriptome at 4 hour post diphtheria toxin administration as the number of sampleing phagocytes was maximal at this time point. We found that one dendritic cell subset (herein refered to as CD103) and two macrophage subsets (herein refered to as CD103 CD11b CD64 and CD11b CD64) were responsible for the sampeling of apoptotic IEC. Cells that sampled were refered to as GFPplus and those that did not were GFPminus. Data represent five independent experiments with 4 mice per experiment and three biological replicates. Less...