The Experts below are selected from a list of 20778 Experts worldwide ranked by ideXlab platform
Semir Beyaz - One of the best experts on this subject based on the ideXlab platform.
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t helper Cell cytokines modulate intestinal stem Cell renewal and differentiation
Cell, 2018Co-Authors: Moshe Biton, Adam L Haber, Noga Rogel, Grace Burgin, Semir Beyaz, Alexandra Schnell, Orr AshenbergAbstract:In the small intestine, a niche of Accessory Cell types supports the generation of mature epithelial Cell types from intestinal stem Cells (ISCs). It is unclear, however, if and how immune Cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-Cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting Cells in co-cultures with CD4+ T helper (Th) Cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory Cells and cytokines reduce it. In vivo genetic perturbation of Th Cells or MHCII expression on Lgr5+ ISCs impacts epithelial Cell differentiation and IEC fate during infection. These interactions between Th Cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.
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t helper Cell cytokines modulate intestinal stem Cell renewal and differentiation
Cell, 2018Co-Authors: Moshe Biton, Adam L Haber, Noga Rogel, Grace Burgin, Semir Beyaz, Alexandra Schnell, Orr AshenbergAbstract:In the small intestine, a niche of Accessory Cell types supports the generation of mature epithelial Cell types from intestinal stem Cells (ISCs). It is unclear, however, if and how immune Cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-Cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting Cells in co-cultures with CD4+ T helper (Th) Cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory Cells and cytokines reduce it. In vivo genetic perturbation of Th Cells or MHCII expression on Lgr5+ ISCs impacts epithelial Cell differentiation and IEC fate during infection. These interactions between Th Cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.
Moshe Biton - One of the best experts on this subject based on the ideXlab platform.
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t helper Cell cytokines modulate intestinal stem Cell renewal and differentiation
Cell, 2018Co-Authors: Moshe Biton, Adam L Haber, Noga Rogel, Grace Burgin, Semir Beyaz, Alexandra Schnell, Orr AshenbergAbstract:In the small intestine, a niche of Accessory Cell types supports the generation of mature epithelial Cell types from intestinal stem Cells (ISCs). It is unclear, however, if and how immune Cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-Cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting Cells in co-cultures with CD4+ T helper (Th) Cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory Cells and cytokines reduce it. In vivo genetic perturbation of Th Cells or MHCII expression on Lgr5+ ISCs impacts epithelial Cell differentiation and IEC fate during infection. These interactions between Th Cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.
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t helper Cell cytokines modulate intestinal stem Cell renewal and differentiation
Cell, 2018Co-Authors: Moshe Biton, Adam L Haber, Noga Rogel, Grace Burgin, Semir Beyaz, Alexandra Schnell, Orr AshenbergAbstract:In the small intestine, a niche of Accessory Cell types supports the generation of mature epithelial Cell types from intestinal stem Cells (ISCs). It is unclear, however, if and how immune Cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-Cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting Cells in co-cultures with CD4+ T helper (Th) Cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory Cells and cytokines reduce it. In vivo genetic perturbation of Th Cells or MHCII expression on Lgr5+ ISCs impacts epithelial Cell differentiation and IEC fate during infection. These interactions between Th Cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.
Orr Ashenberg - One of the best experts on this subject based on the ideXlab platform.
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t helper Cell cytokines modulate intestinal stem Cell renewal and differentiation
Cell, 2018Co-Authors: Moshe Biton, Adam L Haber, Noga Rogel, Grace Burgin, Semir Beyaz, Alexandra Schnell, Orr AshenbergAbstract:In the small intestine, a niche of Accessory Cell types supports the generation of mature epithelial Cell types from intestinal stem Cells (ISCs). It is unclear, however, if and how immune Cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-Cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting Cells in co-cultures with CD4+ T helper (Th) Cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory Cells and cytokines reduce it. In vivo genetic perturbation of Th Cells or MHCII expression on Lgr5+ ISCs impacts epithelial Cell differentiation and IEC fate during infection. These interactions between Th Cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.
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t helper Cell cytokines modulate intestinal stem Cell renewal and differentiation
Cell, 2018Co-Authors: Moshe Biton, Adam L Haber, Noga Rogel, Grace Burgin, Semir Beyaz, Alexandra Schnell, Orr AshenbergAbstract:In the small intestine, a niche of Accessory Cell types supports the generation of mature epithelial Cell types from intestinal stem Cells (ISCs). It is unclear, however, if and how immune Cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-Cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting Cells in co-cultures with CD4+ T helper (Th) Cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory Cells and cytokines reduce it. In vivo genetic perturbation of Th Cells or MHCII expression on Lgr5+ ISCs impacts epithelial Cell differentiation and IEC fate during infection. These interactions between Th Cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.
William E Paul - One of the best experts on this subject based on the ideXlab platform.
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interleukin 12 acts directly on cd4 t Cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Robert A Seder, Ricardo T Gazzinelli, Alan Sher, William E PaulAbstract:Naive CD4+ T Cells produce interleukin 2 (IL-2) but little IL-4 or interferon gamma (IFN-gamma). In vitro, they develop into IL-4 or IFN-gamma producers depending on the conditions of the priming culture. Using T-Cell receptor transgenic CD4+ T Cells, the role of IL-12 and IL-4 in antigen-specific priming was examined. IL-12 substantially enhanced the ability of naive CD4+ T Cells to develop into Cells that produced IFN-gamma upon restimulation. However, it was not essential since anti-IL-12 antibodies failed to block the priming for IFN-gamma observed in the absence of exogenous IL-12. When both IL-12 and IL-4 were present in the priming culture, IL-12 did not inhibit priming for IL-4 production. In contrast, IL-4 diminished but did not abolish priming for IFN-gamma production. In an Accessory Cell-independent priming system, IL-12 strikingly augmented priming for IFN-gamma production, indicating that it acts directly on T Cells. IFN-gamma itself did not enhance priming for IFN-gamma production in either Accessory Cell-dependent or independent systems. In an Accessory Cell-dependent system, the IL-12-mediated enhancement was not blocked by adding neutralizing anti-IFN-gamma monoclonal antibody. However, in an Accessory Cell-independent system, anti-IFN-gamma antibody did inhibit priming for IFN-gamma production leaving open a role for IFN-gamma in the priming process. These data indicate that IL-12 has a major effect on the inductive phase of T-Cell priming by enhancing commitment to IFN-gamma production and thus can profoundly influence the state of immunity that develops.
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interleukin 4 suppresses interleukin 2 and interferon gamma production by naive t Cells stimulated by Accessory Cell dependent receptor engagement
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Toshio Tanaka, J Huli, Robert A Seder, Fazekas B De St Groth, William E PaulAbstract:Interleukin 2 (IL-2) and interferon gamma (IFN-gamma) production by CD4+ T Cells and IFN-gamma production by CD8+ T Cells from naive mice in response to soluble anti-CD3 and antigen-presenting Cells (APCs) were strikingly inhibited by culture in the presence of IL-4. IL-4 decreased IL-2 and IFN-gamma mRNA levels after 15-24 hr but gave relatively little decrease in these mRNAs at 6-12 hr after stimulation with soluble anti-CD3. A 16-hr preculture of T Cells with anti-CD3, APCs, and IL-4 was sufficient to inhibit subsequent production of IL-2 and IFN-gamma in response to restimulation in the absence of IL-4. Furthermore, IL-4 treatment of T Cells purified 24 hr after stimulation inhibited their capacity to subsequently produce IL-2 in response to anti-CD3 and APCs, indicating that T Cells were targets of IL-4-mediated inhibition. IL-4 blocked acute IL-2 production in response to a cytochrome c peptide of T Cells derived from transgenic mice expressing T-Cell receptors specific for cytochrome c but it did not block IL-2 production by such Cells after they had been primed in vitro. Nor did IL-4 inhibit production of IFN-gamma by cloned T Cells in response to antigen and APCs or production of IL-2 and IFN-gamma by naive T Cells in response to phorbol ester and calcium ionophore. These results indicate that IL-4 strikingly inhibits IL-2 and IFN-gamma production by naive T Cells in response to Accessory Cell-dependent, receptor-mediated stimulation (i.e., soluble anti-CD3 and APCs or antigen and APCs) but does not inhibit Accessory Cell-independent stimulation of naive T Cells or Accessory Cell-dependent receptor-mediated stimulation of recently primed T Cells or cloned T-Cell lines.
Miyeon Kim - One of the best experts on this subject based on the ideXlab platform.
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function of cd4 cd3 Cells in relation to b and t zone stroma in spleen
Blood, 2007Co-Authors: Miyeon Kim, Fabrina Gaspal, Fiona M Mcconnell, Lucy S K Walker, Vasilios Bekiaris, Andrea J White, Stephanie H Glanville, Jorge Caamano, Eric J Jenkinson, Graham AndersonAbstract:Lymphocytes from lymphotoxin (LT) α–deficient mice, which lack segregation of their B- and T-Cell areas, acquire normal organization following adoptive transfer into RAG-deficient recipients, identifying a non-B non-T Cell in the segregation process. Here we show that a CD4 + CD3 − Accessory Cell is tightly associated with discrete VCAM-1–expressing stromal Cells in B- and T-Cell areas of the mouse spleen. CD4 + CD3 − Cells express high levels of LTα, LTβ, and tumor necrosis factor (TNF) α, which are the ligands for the LTβ receptor and TNFR1 expressed by stromal Cells. The expression of these ligands is functional, as transferring CD4 + CD3 − Cells derived from either embryonic or adult tissues into LTα-deficient mice organizes B/T segregation and up-regulates CCL21 protein expression in areas where T Cells are segregated from B Cells. We propose that the function of CD4 + CD3 − Cells is to form a link between primed CD4 T Cells and the underlying stromal elements, creating distinct microenvironments in which they enable effector responses.
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neonatal and adult cd4 cd3 Cells share similar gene expression profile and neonatal Cells up regulate ox40 ligand in response to tl1a tnfsf15
Journal of Immunology, 2006Co-Authors: Miyeon Kim, Fabrina Gaspal, Fiona M Mcconnell, Andrea J White, Eric J Jenkinson, Graham Anderson, Kaimichael Toellner, Sonia M Parnell, Peter J. L. LaneAbstract:We report here the quantitative expression of a set of immunity-related genes, including TNF family members, chemokine receptors, and transcription factors, in a CD4+CD3− Accessory Cell. By correlating gene expression between Cell-sorted populations of defined phenotype, we show that the genetic fingerprint of these CD4+CD3− Cells is distinct from dendritic Cells, plasmacytoid dendritic Cells, T Cells, B Cells, and NK Cells. In contrast, it is highly similar to CD4+CD3− Cells isolated from embryonic and neonatal tissues, with the exception that only adult populations express OX40L and CD30L. We have previously reported that IL-7 signals regulate CD30L expression. In the present study, we show that both neonatal and adult CD4+CD3− Cells express the TNF family member, death receptor 3 (TNFRSF25), and that addition of TL1A (TNFSF15), the ligand for death receptor 3, up-regulates OX40L on neonatal CD4+CD3− Cells. Finally, we demonstrate that this differentiation occurs in vivo: neonatal CD4+CD3− Cells up-regulate both CD30L and OX40L after adoptive transfer into an adult recipient.
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mice deficient in ox40 and cd30 signals lack memory antibody responses because of deficient cd4 t Cell memory
Journal of Immunology, 2005Co-Authors: Fabrina Gaspal, Miyeon Kim, Fiona M Mcconnell, Chandra Raykundalia, Vasilios Bekiaris, Peter J. L. LaneAbstract:Recently, we reported that a CD4 + CD3 − CD11c − Accessory Cell provided OX40-dependent survival signals to follicular T Cells. These Accessory Cells express both OX40 ligand and CD30 ligand, and the receptors, OX40 and CD30, are both expressed on Th2-primed CD4 T Cells. OX40 and CD30 signals share common signaling pathways, suggesting that CD30 signals might substantially compensate in OX40-deficient mice. In this report we have dissected the signaling roles of CD30 alone and in combination with OX40. CD30-deficient mice showed an impaired capacity to sustain follicular germinal center responses, and recall memory Ab responses were substantially reduced. Deficiencies in OX40 and CD30 signals were additive; secondary Ab responses were ablated in double-deficient mice. Although the initial proliferation of OX40/CD30 double-knockout OTII transgenic T Cells was comparable to that of their normal counterparts, they failed to survive in vivo, and this was associated with reduced T Cell numbers associated with CD4 + CD3 − Cells in B follicles. Finally, we show that OX40/CD30 double-knockout OTII transgenic T Cells fail to survive compared with normal T Cells when cocultured with CD4 + CD3 − Cells in vitro.
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cd4 cd3 Accessory Cells costimulate primed cd4 t Cells through ox40 and cd30 at sites where t Cells collaborate with b Cells
Immunity, 2003Co-Authors: Miyeon Kim, Fabrina Gaspal, Helen E Wiggett, Fiona M Mcconnell, Adam Gulbransonjudge, Chandra Raykundalia, Lucy S K Walker, Margaret GoodallAbstract:Abstract In this report we identify an Accessory Cell that interacts with primed and memory T Cells at sites where they collaborate with B Cells. These Cells are distinguished from conventional dendritic Cells by their lack of response to Flt3 ligand and their inability to process antigen. Unlike dendritic Cells, the CD4 + CD3 − Cells have little CD80 or CD86 expression but do express high levels of the TNF ligands, OX40 ligand and CD30 ligand. We show that Th2-primed Cells express the receptors for these TNF ligands and preferentially survive when cocultured with these Cells. Furthermore, we show that the preferential survival of OX40 + T Cells and support of memory T Cell help for B Cells are linked to their association with CD4 + CD3 − Cells in vivo.
