Bone marrow monocytes sustain NK cell-poiesis during non-alcoholic steatohepatitis.

Natural killer (NK) cells are the predominant lymphocyte population in the liver. At the onset of non-alcoholic steatohepatitis (NASH), an accumulation of activated NK cells is observed in the liver in parallel with inflammatory monocyte recruitment and an increased systemic inflammation. Using in vivo and in vitro experiments, we unveil a specific stimulation of NK cell-poiesis during NASH by medullary monocytes that trans-present interleukin-15 (IL-15) and secrete osteopontin, a biomarker for patients with NASH.

Spatiotemporal dynamics of cytokines expression dictate fetal liver hematopoiesis.

During embryogenesis, yolk-sac and intra-embryonic-derived hematopoietic progenitors, comprising the precursors of adult hematopoietic stem cells, converge into the fetal liver. With a new staining strategy, we defined all non-hematopoietic components of the fetal liver and found that hepatoblasts are the major producers of hematopoietic growth factors. We identified mesothelial cells, a novel component of the stromal compartment, producing Kit ligand, a major hematopoietic cytokine.

Synergistic prostaglandin E synthesis by myeloid and endothelial cells promotes fetal hematopoietic stem cell expansion in vertebrates.

During development, hematopoietic stem cells (HSCs) are produced from the hemogenic endothelium and will expand in a transient hematopoietic niche. Prostaglandin E (PGE2) is essential during vertebrate development and HSC specification, but its precise source in the embryo remains elusive. Here, we show that in the zebrafish embryo, PGE2 synthesis genes are expressed by distinct stromal cell populations, myeloid (neutrophils, macrophages), and endothelial cells of the caudal hematopoietic tissue.

Identification of fetal liver stroma in spectral cytometry using the parameter autofluorescence.

The fetal liver (FL) is the main hematopoietic organ during embryonic development. The FL is also the unique anatomical site where hematopoietic stem cells expand before colonizing the bone marrow, where they ensure life-long blood cell production and become mostly resting. The identification of the different cell types that comprise the hematopoietic stroma in the FL is essential to understand the signals required for the expansion and differentiation of the hematopoietic stem cells.

Cnidarian Cell Type Diversity and Regulation Revealed by Whole-Organism Single-Cell RNA-Seq.

The emergence and diversification of cell types is a leading factor in animal evolution. So far, systematic characterization of the gene regulatory programs associated with cell type specificity was limited to few cell types and few species. Here, we perform whole-organism single-cell transcriptomics to map adult and larval cell types in the cnidarian Nematostella vectensis, a non-bilaterian animal with complex tissue-level body-plan organization.

Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool.

We investigated the ability of monoclonal B cells to restore primary and secondary T-cell dependent antibody responses in adoptive immune-deficient hosts. Priming induced B cell activation and expansion, AID expression, antibody production and the generation of IgM+IgG- and IgM-IgG+ antigen-experienced B-cell subsets that persisted in the lymphopenic environment by cell division. Upon secondary transfer and recall the IgM-IgG+ cells responded by the production of antigen-specific IgG while the IgM+ memory cells secreted mainly IgM and little IgG, but generated new B cells expressing germinal center markers.

IL-2 coordinates IL-2-producing and regulatory T cell interplay.

Many species of bacteria use quorum sensing to sense the amount of secreted metabolites and to adapt their growth according to their population density. We asked whether similar mechanisms would operate in lymphocyte homeostasis. We investigated the regulation of the size of interleukin-2 (IL-2)-producing CD4(+) T cell (IL-2p) pool using different IL-2 reporter mice.

In vivo and in absence of a thymus, the enforced expression of the Notch ligands delta-1 or delta-4 promotes T cell development with specific unique effects.

The role of Notch signaling in T cell commitment during lymphoid development is well established. However, the identity of the ligand that triggers this critical signal in vivo is still unclear. By overexpressing Delta-1 and Delta-4 ligands in the hemopoietic cells of athymic nu/nu host mice, we demonstrate that, in vivo and in the absence of a thymus, Delta-1 or Delta-4 expression is sufficient to promote T cell development from the most immature progenitor stages to complete maturation of both CD8(+) and CD4(+) alphabeta T cells.