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IRF8 acts in lineage-committed rather than oligopotent progenitors to control neutrophil vs monocyte production.
Roles for IRF8 are identified in regulating progenitor survival and differentiation and preventing leukemic cell accumulation, which shows it does not regulate granulocytic vs monocytic fate in GMPs, but instead acts downstream of lineage commitment to selectively control neutrophil and monocyte production. Expand
Blimp-1 Functions as a Molecular Switch to Prevent Inflammatory Activity in Foxp3+RORγt+ Regulatory T Cells
It is shown that despite their sustained expression of Foxp3, Blimp-1−/− RORγt+IL-17-producing Treg lose suppressor function and can promote intestinal inflammation, indicating that repression of Th17-associated cytokines by Blimps-1 is a crucial requirement for R ORγt-+ Treg function. Expand
Detection of a TLR2 agonist by hematopoietic stem and progenitor cells impacts the function of the macrophages they produce
In vitro and in vivo studies show that macrophages derived from mouse and human HSPC subsets exposed to a TLR2 agonist prior to or during macrophage differentiation produce lower levels of inflammatory cytokines and reactive oxygen species, and this may impact the clinical utility of targeting TLRs on HSPCs to boost myelopoiesis. Expand
Autocrine Type I IFN Signaling in Dendritic Cells Stimulated with Fungal β-Glucans or Lipopolysaccharide Promotes CD8 T Cell Activation
Insight is provided into the mechanisms underlying CD8 T cell activation during infection, which may be useful in the rational design of vaccines directed against pathogens and tumors. Expand
The first trimester human placenta is a site for terminal maturation of primitive erythroid cells.
Findings indicate that placental macrophages may assist the enucleation process of primitive RBCs in placental villi, implying an unexpectedly broad role for the placenta in embryonic hematopoiesis. Expand
564 Potency-reduced and extended half-life IL12 heterodimeric Fc-fusions exhibit strong anti-tumor activity with potentially improved therapeutic index compared to native IL12 agents
Background Interleukin-12 (IL12) is a proinflammatory cytokine produced by activated antigen-presenting cells that induces differentiation of Th1 cells and increased proliferation and cytotoxicity ofExpand
Preclinical data suggests that tumor lysatepulsed DC vaccines can be enhanced by stimulation of Dectin-1 and TLR-9, and the combination of -glucan and CpG was evaluated for enhancing DC vaccines in vivo. Expand