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Full-Text Articles in Cell and Developmental Biology

Delineation Of Precursors In Murine Spleen That Develop In Contact With Splenic Endothelium To Give Novel Dendritic-Like Cells., Jonathan Tan, Pravin Periasamy, Helen O'Neill Sep 2015

Delineation Of Precursors In Murine Spleen That Develop In Contact With Splenic Endothelium To Give Novel Dendritic-Like Cells., Jonathan Tan, Pravin Periasamy, Helen O'Neill

Jonathan Tan

Hematopoietic cell lineages are best described in terms of distinct progenitors with limited differentiative capacity. To distinguish cell lineages, it is necessary to define progenitors and induce their differentiation in vitro. We previously reported in vitro development of immature dendritic-like cells (DCs) in long-term cultures (LTCs) of murine spleen, and in cocultures of spleen or bone marrow (BM) over splenic endothelial cell lines derived from LTCs. Cells produced are phenotypically distinct CD11b(hi)CD11c(lo)CD8(-)MHC-II(-) cells, tentatively named L-DCs. Here we delineate L-DC progenitors as different from known DC progenitors in BM and DC precursors in spleen. The progenitor is contained within the …


Haematopoietic Stem Cells In Spleen Have Distinct Differentiative Potential For Antigen Presenting Cells., Jonathan Tan, Helen O'Neill Sep 2015

Haematopoietic Stem Cells In Spleen Have Distinct Differentiative Potential For Antigen Presenting Cells., Jonathan Tan, Helen O'Neill

Jonathan Tan

Dendritic cells (DC) are known to develop from macrophage dendritic progenitors (MDP) in bone marrow (BM), which give rise to conventional (c)DC and monocytes, both dominant antigen presenting cell (APC) subsets in spleen. This laboratory has however defined a distinct dendritic-like cell subset in spleen (L-DC), which can also be derived in long-term cultures of spleen. In line with the restricted in vitro development of only L-DC in these stromal cultures, we questioned whether self-renewing HSC or progenitors exist in spleen with restricted differentiative capacity for only L-DC. Neonatal spleen and BM were compared for their ability to reconstitute mice …


Concise Review: Dendritic Cell Development In The Context Of The Spleen Microenvironment, Jonathan Tan, Helen O'Neill Sep 2015

Concise Review: Dendritic Cell Development In The Context Of The Spleen Microenvironment, Jonathan Tan, Helen O'Neill

Jonathan Tan

The dendritic cell (DC) population in spleen comprises a mixture of cells including endogenous DC progenitors, DC precursors migrating in from blood and bone marrow, and DC in different states of differentiation and activation. A role for different microenvironments in supporting the dynamic development of murine DC of different types or lineages is considered here. Recent evidence for production of DC dependent on splenic stromal cells is reviewed in the light of evidence that cell production is dependent on cells comprising an endothelial niche in spleen. The possibility that self-renewing progenitors in spleen give rise to DC with tolerogenic or …


Another Armed Cd4(+) T Cell Ready To Battle Hepatocellular Carcinoma, Roniel Cabrera, Gyongyi Szabo Sep 2014

Another Armed Cd4(+) T Cell Ready To Battle Hepatocellular Carcinoma, Roniel Cabrera, Gyongyi Szabo

Gyongyi Szabo

No abstract provided.


Exosome-Mediated Delivery Of Functionally Active Mirna-155 Inhibitor To Macrophages, Fatemeh Momen-Heravi, Shashi Bala, Terence Bukong, Gyongyi Szabo Sep 2014

Exosome-Mediated Delivery Of Functionally Active Mirna-155 Inhibitor To Macrophages, Fatemeh Momen-Heravi, Shashi Bala, Terence Bukong, Gyongyi Szabo

Gyongyi Szabo

Exosomes, membranous nanovesicles, naturally carry bio-macromolecules and play pivotal roles in both physiological intercellular crosstalk and disease pathogenesis. Here, we showed that B cell-derived exosomes can function as vehicles to deliver exogenous miRNA-155 mimic or inhibitor into hepatocytes or macrophages, respectively. Stimulation of B cells significantly increased exosome production. Unlike in parental cells, baseline level of miRNA-155 was very low in exosomes derived from stimulated B cells. Exosomes loaded with a miRNA-155 mimic significantly increased miRNA-155 levels in primary mouse hepatocytes and the liver of miRNA-155 knockout mice. Treatment of RAW macrophages with miRNA-155 inhibitor loaded exosomes resulted in statistically …


Stomatin-Like Protein 2 Deficiency In T Cells Is Associated With Altered Mitochondrial Respiration And Defective Cd4+ T Cell Responses., Darah A Christie, Panagiotis Mitsopoulos, Julianna Blagih, Stanley D Dunn, Julie St-Pierre, Russell G Jones, Grant M Hatch, Joaquín Madrenas Sep 2013

Stomatin-Like Protein 2 Deficiency In T Cells Is Associated With Altered Mitochondrial Respiration And Defective Cd4+ T Cell Responses., Darah A Christie, Panagiotis Mitsopoulos, Julianna Blagih, Stanley D Dunn, Julie St-Pierre, Russell G Jones, Grant M Hatch, Joaquín Madrenas

Stanley D Dunn

Stomatin-like protein 2 (SLP-2) is a mostly mitochondrial protein that regulates mitochondrial biogenesis and function and modulates T cell activation. To determine the mechanism of action of SLP-2, we generated T cell-specific SLP-2-deficient mice. These mice had normal numbers of thymocytes and T cells in the periphery. However, conventional SLP-2-deficient T cells had a posttranscriptional defect in IL-2 production in response to TCR ligation, and this translated into reduced CD4(+) T cell responses. SLP-2 deficiency was associated with impaired cardiolipin compartmentalization in mitochondrial membranes, decreased levels of the NADH dehydrogenase (ubiquinone) iron-sulfur protein 3, NADH dehydrogenase (ubiquinone) 1β subcomplex subunit …


Delineation Of Precursors In Murine Spleen That Develop In Contact With Splenic Endothelium To Give Novel Dendritic-Like Cells., Jonathan Tan, Pravin Periasamy, Helen O'Neill Dec 2009

Delineation Of Precursors In Murine Spleen That Develop In Contact With Splenic Endothelium To Give Novel Dendritic-Like Cells., Jonathan Tan, Pravin Periasamy, Helen O'Neill

Helen O'Neill

Hematopoietic cell lineages are best described in terms of distinct progenitors with limited differentiative capacity. To distinguish cell lineages, it is necessary to define progenitors and induce their differentiation in vitro. We previously reported in vitro development of immature dendritic-like cells (DCs) in long-term cultures (LTCs) of murine spleen, and in cocultures of spleen or bone marrow (BM) over splenic endothelial cell lines derived from LTCs. Cells produced are phenotypically distinct CD11b(hi)CD11c(lo)CD8(-)MHC-II(-) cells, tentatively named L-DCs. Here we delineate L-DC progenitors as different from known DC progenitors in BM and DC precursors in spleen. The progenitor is contained within the …


Haematopoietic Stem Cells In Spleen Have Distinct Differentiative Potential For Antigen Presenting Cells., Jonathan Tan, Helen O'Neill Dec 2009

Haematopoietic Stem Cells In Spleen Have Distinct Differentiative Potential For Antigen Presenting Cells., Jonathan Tan, Helen O'Neill

Helen O'Neill

Dendritic cells (DC) are known to develop from macrophage dendritic progenitors (MDP) in bone marrow (BM), which give rise to conventional (c)DC and monocytes, both dominant antigen presenting cell (APC) subsets in spleen. This laboratory has however defined a distinct dendritic-like cell subset in spleen (L-DC), which can also be derived in long-term cultures of spleen. In line with the restricted in vitro development of only L-DC in these stromal cultures, we questioned whether self-renewing HSC or progenitors exist in spleen with restricted differentiative capacity for only L-DC. Neonatal spleen and BM were compared for their ability to reconstitute mice …


Dendritic Cells As Immune Regulators: The Mouse Model, Kristin Griffiths, Helen O'Neill Dec 2007

Dendritic Cells As Immune Regulators: The Mouse Model, Kristin Griffiths, Helen O'Neill

Helen O'Neill

Dendritic cells (DC) are central to the immune system because of their role in antigen presentation leading to either tolerance or immunity among cells of the adaptive immune response. It is becoming increasingly evident that DC show extensive plasticity in terms of their origin and function, giving rise to a number of subsets represented differentially in all lymphoid organs. This article considers the tolerogenic capacity of murine DC and draws a distinction between DC that induce tolerance in the immature state and immunity in an inflammatory context, and those that act as regulatory cells inducing immunosuppression in the presence of …


Expression Of T-Cell Receptor Genes During Early T-Cell Development, Janice Abbey, Helen O'Neill Dec 2007

Expression Of T-Cell Receptor Genes During Early T-Cell Development, Janice Abbey, Helen O'Neill

Helen O'Neill

Lymphoid cell development is an ordered process that begins in the embryo in specific sites and progresses through multiple differentiative steps to production of T- and B-cells. Lymphoid cell production is marked by the rearrangement process, which gives rise to mature cells expressing antigen-specific T-cell receptors (TCR) and immunoglobulins (Ig). While most transcripts arising from TCR or Ig loci reflect fully rearranged genes, germline transcripts have been identified, but these have always been thought to have no specific purpose. Germline transcription from either unrearranged TCR or unrearranged Ig loci was commonly associated with an open chromatin configuration during VDJ recombination. …


Concise Review: Dendritic Cell Development In The Context Of The Spleen Microenvironment, Jonathan Tan, Helen O'Neill Dec 2006

Concise Review: Dendritic Cell Development In The Context Of The Spleen Microenvironment, Jonathan Tan, Helen O'Neill

Helen O'Neill

The dendritic cell (DC) population in spleen comprises a mixture of cells including endogenous DC progenitors, DC precursors migrating in from blood and bone marrow, and DC in different states of differentiation and activation. A role for different microenvironments in supporting the dynamic development of murine DC of different types or lineages is considered here. Recent evidence for production of DC dependent on splenic stromal cells is reviewed in the light of evidence that cell production is dependent on cells comprising an endothelial niche in spleen. The possibility that self-renewing progenitors in spleen give rise to DC with tolerogenic or …


Splenic Endothelial Cell Lines Support Development Of Dendritic Cells From Bone Marrow, Geneviève Despars, Helen O'Neill May 2006

Splenic Endothelial Cell Lines Support Development Of Dendritic Cells From Bone Marrow, Geneviève Despars, Helen O'Neill

Helen O'Neill

Although growth factors are commonly used to generate dendritic cells (DCs) in vitro, the role of the microenvironment necessary for DC development is still poorly understood. The mixed splenic stromal cell population STX3 defines an in vitro microenvironment supportive of DC development. Dissection of cellular components of the STX3 stroma should provide information about a niche for DC development. STX3 was therefore cloned by single-cell sorting, and a panel of 102 splenic stromal cell lines was established. Four representative splenic stromal cell lines that support hematopoiesis from bone marrow are described here in terms of stromal cell type and DC …