Speaker
Description
The alarmins S100A8 and S100A9 are important signaling molecules during the innate immune response of monocytes and neutrophils. Indeed, S100A8 and S100A9 are dys-regulated in numerous tumors and inflammatory diseases. To gain insights into mechanisms of transcriptional regulation of S100A8/A9, four candidate transcription factors were tested for their impact on S100A8/A9 expression in murine monocytes and granulocytes obtained from transiently immortalized myeloid stem cells (ER-Hoxb8 cells). The recent CRISPR/Cas9 genome editing system that is able to precisely cleave desired gene locations was used to generate candidate transcription-factor specific-knock-out ER-Hoxb8 cell lines. Further knock-out cell lines were obtained by generating ER-Hoxb8 cells of bone marrow derived cells from transgenic mice. Analysis of S100A8/A9 expression during differentiation of knock-out cell lines identified, inter alia, ATF3 as a potential negative regulator of these alarmins in monocytes. Interestingly, the bile acid receptor FXR was suggested to be a positive regulator of S100A8/A9 in this study in both, monocytes and neutrophils. Analysis also revealed C/EBPδ as a positive regulator of S100A8/A9 in ER-Hoxb8 neutrophils. Through these findings we took a step forward in understanding mechanisms behind transcriptional regulation of S100A8 and S100A9.
