Project description:The goal of this study was to compare transcriptional changes, on the single cell level, in splenic monocytes evoked by global IL-17A/F deficiency
Project description:Gene profiling of CNS-derived microglia vs splenic CD11b+Ly6C+ monocyte subsets deom adult mice Gene array identified 1572 genes that were enriched in microglia vs. 611 monocyte enriched genes with a greater than 5-fold difference (P<0.001). Gene profiling of CD11b+CD45Low microglia isolated from the CNS and CD11b+Ly6C+ monocyte subsets isolated from the spleen of naM-CM-/ve adult mice.
Project description:We show that monocyte development is accompanied by stepwise RNA expression changes and that Ly6C+ monocytes upon transfer develop into Ly6C- monocytes indicated by a comparable expression profile to host Ly6C- monocytes
Project description:Chromatin status of murine blood Ly6C+ and Ly6C- monocytes indicates that both population share K4me3 marks (promoters) while Ly6C- monocytes establish de novo enhancers (K4me1, K4me2) during differentiation
Project description:Administration of G-CSF mobilizes a unique population of CD11b+Ly6C+CD34+mature monocytes that can inhibit GVHD in murine models of BMT via an iNOS-dependent mechanism. The transcriptional profiles of flow sorted lineage-CD11b+CD34+ cells from G-CSF treated mice were compared with conventional splenic Ly6C+ and Ly6C- monocytes, progenitor cells and cultured myeloid-derived suppressor cells. Further comparisons were made with lineage-CD11b+CD34+ cells from G-CSF treated mice that had been grown in culture or that were derived from iNOS ko mice. We used microarrays to detail the global programme of gene expression underlying diffrenetiation of each of these cell types
Project description:Loss-of-function mutations in the lysosomal nucleoside transporter SLC29A3 lead to the accumulation of nucleosides in lysosomes and result in histiocytosis, characterized by the excessive accumulation of phagocytes in multiple organs. However, the underlying mechanism by which lysosomal nucleoside storage drives histiocytosis remains poorly understood. Herein, we provide evidence that histiocytosis in Slc29a3–/– mice is dependent on Toll-like receptor 7 (TLR7), which senses a combination of guanosines and oligoribonucleotides. TLR7 increased phagocyte populations by driving the proliferation of immature Ly6C high splenic macrophages and their subsequent maturation into Ly6C low phagocytes in Slc29a3–/– mice. Interestingly, TLR7 activation in nucleoside-laden splenic macrophages failed to induce inflammatory responses. Our data demonstrate that TLR7 responses to lysosomal nucleoside stress drive unique immune responses distinct from inflammation in SLC29A3-related disorders.
Project description:Administration of G-CSF mobilizes a unique population of CD11b+Ly6C+CD34+mature monocytes that can inhibit GVHD in murine models of BMT via an iNOS-dependent mechanism. The transcriptional profiles of flow sorted lineage-CD11b+CD34+ cells from G-CSF treated mice were compared with conventional splenic Ly6C+ and Ly6C- monocytes, progenitor cells and cultured myeloid-derived suppressor cells. Further comparisons were made with lineage-CD11b+CD34+ cells from G-CSF treated mice that had been grown in culture or that were derived from iNOS ko mice. We used microarrays to detail the global programme of gene expression underlying diffrenetiation of each of these cell types Lin-CD11b+CD34+ populations were isolated directly from the spleens of G-CSF-treated C57BL/6 mice or iNOS ko mice. In untreated C57BL/6 mice, Lin-CD11b+CD115+Ly6C+ and Lin-CD11b+CD115+Ly6C- monocytes were isolated from the spleen and Lin-CD117+CD115+CD135-Ly6C+CD11b- common monocyte progenitors were isolated from the bone marrow. Myeloid-derived suppressor cells (Ly6C+CD11b+ cells derived from G-CSF, GM-CSF and IL-13 cultured C57BL/6 bone marrow) were also isolated and compared with the above populations. Lin-CD11b+CD34+ spleen cells derived from G-CSF-treated C57BL/6 mice were cultured for 3 days in Flt3 ligand and SCF and then compared to the original input population.