scholarly journals Spleen as a Site for Hematopoiesis of a Distinct Antigen Presenting Cell Type

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Helen C. O'Neill ◽  
Kristin L. Griffiths ◽  
Pravin Periasamy ◽  
Rebecca A. Hinton ◽  
Ying-Ying Hey ◽  
...  
Keyword(s):  
Specific Antigen ◽  
Myeloid Cell ◽  
Antigen Presenting Cells ◽  
Cell Types ◽  
The Novel ◽  
Cell Type ◽  
Hematopoietic Stem ◽  
Secondary Tissue ◽  
A Site ◽  
Antigen Presenting

While spleen and other secondary tissue sites contribute to hematopoiesis, the nature of cells produced and the environment under which this happens are not fully defined. Evidence is reviewed here for hematopoiesis occurring in the spleen microenvironment leading to the production of tissue-specific antigen presenting cells. The novel dendritic-like cell identified in spleen is phenotypically and functionally distinct from other described antigen presenting cells. In order to identify these cells as distinct, it has been necessary to show that their lineage origin and progenitors differ from that of other known dendritic and myeloid cell types. The spleen therefore represents a distinct microenvironment for hematopoiesis of a novel myeloid cell arising from self-renewing hematopoietic stem cells (HSC) or progenitors endogenous to spleen.

scholarly journals TLR2 and Dectin-1 Signaling in Mouse Hematopoietic Stem and Progenitor Cells Impacts the Ability of the Antigen Presenting Cells They Produce to Activate CD4 T Cells

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1317 ◽  
Author(s):  
Alba Martínez ◽  
Cristina Bono ◽  
Daniel Gozalbo ◽  
Helen S. Goodridge ◽  
M. Luisa Gil ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Antigen Presenting Cells ◽  
Proinflammatory Cytokine Production ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Antigen Presenting ◽  
The Impact

Microbial recognition by pattern recognition receptors (PRRs) expressed on hematopoietic stem and progenitor cells (HSPCs) not only activates myelopoiesis but also programs the function of the monocytes and macrophages they produce. For instance, changes in HSPC programming modify the ability of macrophages derived from them to produce inflammatory cytokines. While HSPCs exposed to a TLR2 agonist give rise to tolerized macrophages (lower proinflammatory cytokine production), HSPCs treated with Dectin-1 ligands produce trained macrophages (higher proinflammatory cytokine production). However, nothing is known about the impact of HSPC exposure to microbes on the function of antigen presenting cells (APCs). In this study we evaluated whether treatment of murine bone marrow HSPCs with a TLR2 or Dectin-1 ligand impacts the antigen presenting capacity of APCs derived from them in vitro. Following activation with microbial ligands or Candida albicans yeasts, APCs derived from TLR2/Dectin-1-programed HSPCs exhibit altered expression of MHCII (signal 1), co-stimulatory molecules (CD40, CD80 and CD86; signal 2) and cytokines (TNF-α, IL-6, IL-12 p40 and IL-2; signal 3). Moreover, APCs derived from TLR2/Dectin-1-programed HSPCs prime enhanced Th1 and Th17 responses, which are important for antifungal defense, in CD4 T cell cocultures. Overall, these results demonstrate for the first time that microbial detection by bone marrow HSPCs can modulate the adaptive immune response by inducing the production of APCs with an altered phenotype.

Adhesion of human T cells to antigen-presenting cells through SIRPβ2-CD47 interaction costimulates T-cell proliferation

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2421-2427 ◽  
Author(s):  
Laura Piccio ◽  
William Vermi ◽  
Kent S. Boles ◽  
Anja Fuchs ◽  
Carey A. Strader ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Antigen Presenting Cells ◽  
Cell Types ◽  
Orphan Receptor ◽  
T Cell Proliferation ◽  
Central Nervous Systems ◽  
And Function ◽  
Antigen Presenting

AbstractSignal-regulatory proteins (SIRPs) are transmembrane glycoproteins belonging to the immunoglobulin (Ig) superfamily that are expressed in the immune and central nervous systems. SIRPα binds CD47 and inhibits the function of macrophages, dendritic cells, and granulocytes, whereas SIRPβ1 is an orphan receptor that activates the same cell types. A recently identified third member of the SIRP family, SIRPβ2, is as yet uncharacterized in terms of expression, specificity, and function. Here, we show that SIRPβ2 is expressed on T cells and activated natural killer (NK) cells and, like SIRPα, binds CD47, mediating cell-cell adhesion. Consequently, engagement of SIRPβ2 on T cells by CD47 on antigen-presenting cells results in enhanced antigen-specific T-cell proliferation.

scholarly journals Modeling and Visualizing Cell Type Switching

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Ahmadreza Ghaffarizadeh ◽  
Gregory J. Podgorski ◽  
Nicholas S. Flann
Keyword(s):  
Expression Profiles ◽  
Control Cell ◽  
Three Dimensional ◽  
Myeloid Cell ◽  
Cell Types ◽  
State Transitions ◽  
Cell Type ◽  
New Approach ◽  
Gene Expression Noise ◽  
Lineage Trees

Understanding cellular differentiation is critical in explaining development and for taming diseases such as cancer. Differentiation is conventionally represented using bifurcating lineage trees. However, these lineage trees cannot readily capture or quantify all the types of transitions now known to occur between cell types, including transdifferentiation or differentiation off standard paths. This work introduces a new analysis and visualization technique that is capable of representing all possible transitions between cell states compactly, quantitatively, and intuitively. This method considers the regulatory network of transcription factors that control cell type determination and then performs an analysis of network dynamics to identify stable expression profiles and the potential cell types that they represent. A visualization tool calledCellDiff3Dcreates an intuitive three-dimensional graph that shows the overall direction and probability of transitions between all pairs of cell types within a lineage. In this study, the influence of gene expression noise and mutational changes during myeloid cell differentiation are presented as a demonstration of theCellDiff3Dtechnique, a new approach to quantify and envision all possible cell state transitions in any lineage network.

scholarly journals Deconvolving sequence features that discriminate between overlapping regulatory annotations

2017 ◽  
Author(s):  
Akshay Kakumanu ◽  
Silvia Velasco ◽  
Esteban Mazzoni ◽  
Shaun Mahony
Keyword(s):  
Embryonic Stem ◽  
Cell Types ◽  
The Novel ◽  
Cell Type ◽  
Dynamic Binding ◽  
Specific Sequence ◽  
Sequence Features ◽  
Binding Behavior ◽  
Distinct Sequence ◽  
Regulatory Sites

AbstractGenomic loci with regulatory potential can be identified and annotated with various properties. For example, genomic sites may be annotated as being bound by a given transcription factor (TF) in one or more cell types. The same sites may be further labeled as being proximal or distal to known promoters. Given such a collection of labeled sites, it is natural to ask what sequence features are associated with each annotation label. However, discovering such label-specific sequence features is often confounded by overlaps between annotation labels; e.g. if regulatory sites specific to a given cell type are also more likely to be promoter-proximal, it is difficult to assess whether motifs identified in that set of sites are associated with the cell type or associated with promoters. In order to meet this challenge, we developed SeqUnwinder, a principled approach to deconvolving interpretable discriminative sequence features associated with overlapping annotation labels. We demonstrate the novel analysis abilities of SeqUnwinder using three examples. Firstly, we show SeqUnwinder’s ability to unravel sequence features associated with the dynamic binding behavior of TFs during motor neuron programming from features associated with chromatin state in the initial embryonic stem cells. Secondly, we characterize distinct sequence properties of multi-condition and cell-specific TF binding sites after controlling for uneven associations with promoter proximity. Finally, we demonstrate the scalability of SeqUnwinder to discover cell-specific sequence features from over one hundred thousand genomic loci that display DNase I hypersensitivity in one or more ENCODE cell lines.Availabilityhttps://github.com/seqcode/sequnwinder

scholarly journals Gas6 deficiency in recipient mice of allogeneic transplantation alleviates hepatic graft-versus-host disease

Blood ◽  
2010 ◽  
Vol 115 (16) ◽  
pp. 3390-3397 ◽  
Author(s):  
Laurent Burnier ◽  
François Saller ◽  
Linda Kadi ◽  
Anne C. Brisset ◽  
Rocco Sugamele ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Antigen Presenting Cells ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Antigen Presenting

Abstract Growth arrest-specific gene 6 (Gas6) is expressed in antigen-presenting cells and endothelial cells (ECs) but not in T cells. When wild-type (WT) or Gas6−/− mice received allogeneic non–T cell–depleted bone marrow cells, hepatic graft-versus-host disease (GVHD) was alleviated in Gas6−/− recipients regardless of donor genotype, but not in WT recipients. T-cell infiltration was more prominent and diffuse in WT than in Gas6−/− recipients' liver. When mice received 0.5 × 106 allogeneic T cells with T cell–depleted allogeneic bone marrow, clinical signs indicated that GVHD was less severe in Gas6−/− than in WT recipients, as shown by a significant improvement of the survival and reduced liver GVHD. These data demonstrate that donor cells were not involved in the protection mechanism. In addition, lack of Gas6 in antigen-presenting cells did not affect WT or Gas6−/− T-cell proliferation. We therefore assessed the response of WT or Gas6−/− ECs to tumor necrosis factor-α. Lymphocyte transmigration was less extensive through Gas6−/− than WT ECs and was not accompanied by increases in adhesion molecule levels. Thus, the lack of Gas6 in ECs impaired donor T-cell transmigration into the liver, providing a rationale for considering Gas6 pathway as a potential nonimmunosuppressive target to minimize GVHD in patients receiving allogeneic hematopoietic stem cell transplantation.

The Allantois and Chorion, Isolated before Chorio-Allantoic Fusion, Have Hematopoietic Potential.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3609-3609
Author(s):  
Brandon M. Zeigler ◽  
Sugiyama Daisuke ◽  
Y. Guo ◽  
Downs M. Karen ◽  
Speck A. Nancy
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Myeloid Cell ◽  
Primitive Streak ◽  
Temporal Analysis ◽  
Hematopoietic Stem ◽  
Spatial And Temporal Analysis ◽  
Chorionic Plate ◽  
Cell Niche ◽  
A Site

Abstract The chorio-allantoic placenta provides for the exchange of nutrients, gas, and waste between the fetus and mother. The murine placenta is also enriched for long term repopulating hematopoietic stem cells, and is therefore a stem cell niche (Gekas et al. Dev. Cell8, 365, 2005 and Ottersbach et al. Dev. Cell8, 377, 2005). However, it is not known if the placenta is colonized by hematopoietic stem cells that originate from other sites in the conceptus, or whether the placenta itself is also a site of hematopoietic cell emergence. The placenta is formed through the fusion of the allantois, a mesodermal extension from the primitive streak, with the chorionic plate, which is comprised of extraembryonic ectoderm and mesoderm. Here we show that the allantois and chorion, isolated before chorio-allantoic fusion and prior to the establishment of circulation, contain hematopoietic potential. Both allantois and chorion explants produced CD45 positive cells, some of which also expressed Mac-1 and Gr-1, when cultured on OP9 stromal cells in the presence of cytokines that promote myeloid cell differentiation. Cultures of allantois and chorion explants in the presence of lymphoid promoting cytokines induced B220 and CD19 positive B cells. Spatial and temporal analysis of Runx1, a marker for definitive hematopoiesis, showed Runx1 is not expressed in either the allantois or the chorion prior to fusion, but is expressed at the base of the allantois and at the chorio-allantoic junction following fusion. Both allantoic explant cultures, and cultures of whole embryos from which allantoises were removed in order to prohibit chorio-allantoic fusion showed that Runx1 expression in neither tissue is dependent upon fusion. We conclude that the allantois and chorion have intrinsic hematopoietic potential prior to the establishment of circulation. Our results furthermore suggest that the placenta is both a niche and a source of hematopoietic cells.

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