Project description:GM-CSF controls the development of granulocytes but little is known about the contribution of the downstream mediating transcription factor STAT5A/B. To elucidate this pathway, we generated mice lacking the Stat5a and 5b genes in blood cells. Peripheral neutrophils were decreased and administration of 5-FU and GM-CSF failed to induce granulopoiesis in Stat5a/b-mutant mice. CMPs were isolated and cultured with GM-CSF.
Project description:GM-CSF controls the development of granulocytes but little is known about the contribution of the downstream mediating transcription factor STAT5A/B. To elucidate this pathway, we generated mice lacking the Stat5a and 5b genes in blood cells. Peripheral neutrophils were decreased and administration of 5-FU and GM-CSF failed to induce granulopoiesis in Stat5a/b-mutant mice. CMPs were isolated and cultured with GM-CSF. Experiment Overall Design: Microarray Experiments for mice lacking or with the Stat5a and 5b genes in blood cells that were treated w/o CMP
Project description:GM-CSF controls the development of granulocytes but little is known about the contribution of the downstream mediating transcription factor STAT5A/B. To elucidate this pathway, we generated mice lacking the Stat5a and 5b genes in blood cells. Peripheral neutrophils were decreased and administration of 5-FU and GM-CSF failed to induce granulopoiesis in Stat5a/b-mutant mice. GMPs were isolated and cultured with GM-CSF. Both the number and size of STAT5A/B-null colonies were reduced and GM-CSF-induced survival of mature STAT5A/B-null neutrophils was impaired. Time-lapse cinematography and single cell tracking of GMPs revealed that STAT5A/B-null cells were characterized by a longer generation time and an increased cell death. Gene expression profiling experiments suggested that STAT5A/B directs GM-CSF signaling through the regulation of cell survival genes.
Project description:GM-CSF controls the development of granulocytes but little is known about the contribution of the downstream mediating transcription factor STAT5A/B. To elucidate this pathway, we generated mice lacking the Stat5a and 5b genes in blood cells. Peripheral neutrophils were decreased and administration of 5-FU and GM-CSF failed to induce granulopoiesis in Stat5a/b-mutant mice. GMPs were isolated and cultured with GM-CSF. Both the number and size of STAT5A/B-null colonies were reduced and GM-CSF-induced survival of mature STAT5A/B-null neutrophils was impaired. Time-lapse cinematography and single cell tracking of GMPs revealed that STAT5A/B-null cells were characterized by a longer generation time and an increased cell death. Gene expression profiling experiments suggested that STAT5A/B directs GM-CSF signaling through the regulation of cell survival genes. Experiment Overall Design: Mice lacking or with the Stat5a and 5b genes in blood cells, which were treated w/o GMP
Project description:Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. Multiple factors including cytokines, transcription factors and multiple signaling pathways are involved in MDSC differentiation. Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin(IL-6) etc could in vitro mediate development of MDSCs.IL-6 with GM-CSF mediated MDSC not only had stronger suppressive function but also the dynamics of their suppressive function was different from GM-CSF alone mediated MDSCs.To found a new regulatory factor (s) in tumor and inflammatory environments, we compared GM-CSF and IL-6 mediated MDSCs with GM-CSF alone mediated MDSCs using lncRNA microarray and protein-coding mRNA microarrays.
Project description:Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. Multiple factors including cytokines, transcription factors and multiple signaling pathways are involved in MDSC differentiation. Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin(IL-6) etc could in vitro mediate development of MDSCs.IL-6 with GM-CSF mediated MDSC not only had stronger suppressive function but also the dynamics of their suppressive function was different from GM-CSF alone mediated MDSCs.To found a new regulatory factor (s) in tumor and inflammatory environments, we compared GM-CSF and IL-6 mediated MDSCs with GM-CSF alone mediated MDSCs using lncRNA microarray, miRNA microarrays and protein-coding mRNA microarrays.
Project description:GM-CSF is involved in immune complex (IC)-mediated arthritis. However, little is known about what is the cellular source of GM-CSF and how it is regulated during IC-mediated inflammation. Using novel GM-CSF reporter mice, we show that NK cells produce GM-CSF during an IC-mediated model of inflammatory arthritis. NK cells promoted STIA in a GM-CSF-dependent manner, as deletion of NK cells and selective removal of GM-CSF production by NK cells abrogated disease. Furthermore, we show that myeloid cell activation by GM-CSF is restrained by induction of JAK/STAT checkpoint inhibitor cytokine-inducible SH2-containing protein, CIS. Myeloid cells from CIS-deficient mice had exaggerated responses to GM-CSF, and these mice develop exacerbated STIA. Our data suggest that tissue NK cells may amplify joint inflammation in arthritis via GM-CSF production and thus represent a novel target in IC-mediated pathology. Endogenous CIS provides a key brake on signaling through the GM-CSF receptor and strategies that boost its function may provide an alternative anti-inflammatory approach.
Project description:Pseudomonas aeruginosa PAO1 persister and normal cells were treated with and without Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) to understand the effect of GM-CSF on gene expression of PAO1. We used DNA microarrays to identify the down-regulated and up-regulated genes after GM-CSF treatment.