Distinct Progenitor Origin Distinguishes a Lineage of Dendritic-Like Cells in Spleen

Petvises, Sawang; O’Neill, Helen C.

doi:10.3389/fimmu.2013.00501

Cited by 17 publications

(95 citation statements)

References 34 publications

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“…After 28 days, co-cultures established with boo/boo Lin - bone marrow yielded significantly higher numbers of both L-DC and cDC-like progeny than WT (Fig 7B). It was previously found that the L-DC progenitor was contained within subsets of LT-HSCs and MPPs [28], while the progenitor of cDC-like cells was contained within CDP and MDP subsets [28]. These results are consistent with evidence for higher numbers of these progenitors in boo/boo over WT bone marrow (Figs 3B and 4B).…”

Section: Resultssupporting

confidence: 88%

“…A number of studies now equate L-DC progenitors with LT-HSC and MPP subsets in bone marrow, fetal liver, and spleen [26, 28, 38]. In order to compare the prevalence of L-DC progenitors in boo/boo versus WT mice, Lin - bone marrow was prepared and seeded into splenic stromal co-cultures as previously described [27, 34, 35].…”

Section: Resultsmentioning

confidence: 99%

“…This procedure has been described in detail previously [27, 28, 34, 35]. Medium change was performed every 3–4 days by replacement of 2.5 ml medium.…”

Section: Methodsmentioning

confidence: 99%

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Impact of the c-MybE308G mutation on mouse myelopoiesis and dendritic cell development

et al. 2017

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Booreana mice carrying the c-Myb308G point mutation were analyzed to determine changes in early hematopoiesis in the bone marrow and among mature cells in the periphery. This point mutation led to increased numbers of early hematopoietic stem and progenitor cells (HSPCs), with a subsequent reduction in the development of B cells, erythroid cells, and neutrophils, and increased numbers of myeloid cells and granulocytes. Myelopoiesis was further investigated by way of particular subsets affected. A specific question addressed whether booreana mice contained increased numbers of dendritic-like cells (L-DC subset) recently identified in the spleen, since L-DCs arise in vitro by direct differentiation from HSPCs co-cultured over splenic stroma. The non-lethal c-Myb mutation in booreana mice was associated with significantly lower representation of splenic CD8- conventional dendritic cells (cDCs), inflammatory monocytes, and neutrophils compared to wild-type mice. This result confirmed the bone marrow origin of progenitors for these subsets since c-Myb is essential for their development. Production of L-DCs and resident monocytes was not affected by the c-MybE308G mutation. These subsets may derive from different progenitors than those in bone marrow, and are potentially established in the spleen during embryogenesis. An alternative explanation may be needed for why there was no change in CD8+ cDCs in booreana spleen since these cells are known to derive from common dendritic progenitors in bone marrow.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

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Impact of the c-MybE308G mutation on mouse myelopoiesis and dendritic cell development

et al. 2017

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“…Methods used for antibody staining and flow cytometry for analysis of cell surface marker expression have been described previously [10, 33, 34]. Prior to antibody staining, non-specific antibody binding to cells was inhibited by absorption of anti-CD16/32 (FcBlock: Biolegend: San Diego, CA, USA) used at 5 μg/10 6 cells in 1 mL of FACS buffer.…”

Section: Methodsmentioning

confidence: 99%

Antigen presenting capacity of murine splenic myeloid cells

2017

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BackgroundThe spleen is an important site for hematopoiesis. It supports development of myeloid cells from bone marrow-derived precursors entering from blood. Myeloid subsets in spleen are not well characterised although dendritic cell (DC) subsets are clearly defined in terms of phenotype, development and functional role. Recently a novel dendritic-like cell type in spleen named ‘L-DC’ was distinguished from other known dendritic and myeloid cells by its distinct phenotype and developmental origin. That study also redefined splenic eosinophils as well as resident and inflammatory monocytes in spleen.ResultsL-DC are shown to be distinct from known splenic macrophages and monocyte subsets. Using a new flow cytometric procedure, it has been possible to identify and isolate L-DC in order to assess their functional competence and ability to activate T cells both in vivo and in vitro. L-DC are readily accessible to antigen given intravenously through receptor-mediated endocytosis. They are also capable of CD8+ T cell activation through antigen cross presentation, with subsequent induction of cytotoxic effector T cells. L-DC are MHCII− cells and unable to activate CD4+ T cells, a property which clearly distinguishes them from conventional DC. The myeloid subsets of resident monocytes, inflammatory monocytes, neutrophils and eosinophils, were found to have varying capacities to take up antigen, but were uniformly unable to activate either CD4+ T cells or CD8+ T cells.ConclusionThe results presented here demonstrate that L-DC in spleen are distinct from other myeloid cells in that they can process antigen for CD8+ T cell activation and induction of cytotoxic effector function, while both L-DC and myeloid subsets remain unable to activate CD4+ T cells. The L-DC subset in spleen is therefore distinct as an antigen presenting cell.

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“…Previously we showed that “L‐DC” can develop in vitro from hematopoietic stem cells (HSC) overlaid above splenic stroma . During inflammation, the binding of pathogen molecules to Toll‐like receptors (TLR) on HSC can trigger differentiation .…”

Section: Resultsmentioning

confidence: 99%

A novel myeloid cell in murine spleen defined through gene profiling

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O'Neill

O’Neill

2019

J Cellular Molecular Medi

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A novel myeloid antigen presenting cell can be generated through in vitro haematopoiesis in long‐term splenic stromal cocultures. The in vivo equivalent subset was recently identified as phenotypically and functionally distinct from the spleen subsets of macrophages, conventional (c) dendritic cells (DC), resident monocytes, inflammatory monocytes and eosinophils. This novel subset which is myeloid on the basis of cell surface phenotype, but dendritic‐like on the basis of cell surface marker expression and antigen presenting function, has been tentatively labelled “L‐DC.” Transcriptome analysis has now been employed to determine the lineage relationship of this cell type with known splenic cDC and monocyte subsets. Principal components analysis showed separation of “L‐DC” and monocytes from cDC subsets in the second principal component. Hierarchical clustering then indicated a close lineage relationship between this novel subset, resident monocytes and inflammatory monocytes. Resident monocytes were the most closely aligned, with no genes specifically expressed by the novel subset. This subset, however, showed upregulation of genes reflecting both dendritic and myeloid lineages, with strong upregulation of several genes, particularly CD300e. While resident monocytes were found to be dependent on Toll‐like receptor signalling for development and were reduced in number in Myd88 ‐/‐ and Trif ‐/‐ mutant mice, both the novel subset and inflammatory monocytes were unaffected. Here, we describe a novel myeloid cell type closely aligned with resident monocytes in terms of lineage but distinct in terms of development and functional capacity.

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Distinct Progenitor Origin Distinguishes a Lineage of Dendritic-Like Cells in Spleen

Cited by 17 publications

References 34 publications

Impact of the c-MybE308G mutation on mouse myelopoiesis and dendritic cell development

Impact of the c-MybE308G mutation on mouse myelopoiesis and dendritic cell development

Antigen presenting capacity of murine splenic myeloid cells

A novel myeloid cell in murine spleen defined through gene profiling

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