The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Steffen Jung - One of the best experts on this subject based on the ideXlab platform.
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securing the immune tightrope mononuclear phagocytes in the intestinal Lamina Propria
Nature Reviews Immunology, 2010Co-Authors: Chen Varol, Ehud Zigmond, Steffen JungAbstract:Several distinct populations of dendritic cells and macrophages are found in the intestinal Lamina Propria; these cells have crucial roles in both tolerogenic and inflammatory-type immune responses at the mucosa. This Review describes the recent findings that have increased our understanding of the origin and functions of intestinal mononuclear phagocytes.
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transepithelial pathogen uptake into the small intestinal Lamina Propria
Journal of Immunology, 2006Co-Authors: Alexandra Valloneberhard, Limor Landsman, Nir Yogev, Bernard Verrier, Steffen JungAbstract:The Lamina Propria that underlies and stabilizes the gut lining epithelium is densely populated with strategically located mononuclear phagocytes. Collectively, these Lamina Propria macrophages and dendritic cells (DC) are believed to be crucial for tissue homeostasis as well as the innate and adaptive host defense. Lamina Propria DC were recently shown to gain direct access to the intestinal lumen by virtue of epithelium-penetrating dendrites. However, the role of these structures in pathogen uptake remains under debate. In this study, we report that entry of a noninvasive model pathogen (Aspergillus fumigatus conidia) into the murine small intestinal Lamina Propria persists in the absence of either transepithelial dendrites or Lamina Propria DC and macrophages. Our results suggest the existence of multiple pathogen entry pathways and point at the importance of villus M cells in the uptake of gut lumen Ags. Interestingly, transepithelial dendrites seem altogether absent from the small intestine of BALB/c mice suggesting that the function of Lamina Propria DC extensions resides in their potential selectivity for luminal Ags, rather than in general uptake or gut homeostasis.
Kenya Honda - One of the best experts on this subject based on the ideXlab platform.
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Mechanism of Th17 cell differentiation in the intestinal Lamina Propria
Inflammation and Regeneration, 2009Co-Authors: Koji Atarashi, Kiyoshi Takeda, Kenya HondaAbstract:IL-17-producing Th17 cells are a subset of CD4+ T cells that have been implicated in various chronic inflammatory and autoimmune diseases. Th17 cells selectively and constitutively reside in the intestinal Lamina Propria. Recent studies using germ-free mice indicate that the development of Lamina Propria Th17 cells are dependent on the stimulation by intestinal commensal bacteria. In this review, we summarize the recent advances in our understanding of the mechanisms of intestinal Th17 synthesis in mice. We also propose a model in which commensal bacteria-derived factors, including ATP, activate a unique subset of dendritic cells, leading to the differentiation of Th17 cells in the intestinal Lamina Propria in situ.
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atp drives Lamina Propria th17 cell differentiation
Nature, 2008Co-Authors: Koji Atarashi, Tatsuichiro Shima, Masaharu Onoue, Richard J. Evans, Jun-ichi Nishimura, Yoshinori Umesaki, Naoto Ishii, Hideo Yagita, Masahiro Yamamoto, Kenya HondaAbstract:The intestinal Lamina Propria, a layer of cells forming part of the mucous membrane, boasts a complicated mix of cell populations, including the selective presence of TH17 or T helper 17 cells, the subset of T helpers that produces interleukin 17. A study in mice now shows that commensal bacteria activate a unique subset of intestinal dendritic cells to induce interleukin-6 production and TGF-beta activation, thereby promoting the local differentiation of TH17 cells. It is the ATP that the bacteria produce that promotes this effect. This finding highlights the importance of commensal bacteria and ATP in immuno-logical diseases, and may help in determining the mechanisms by which aberrant TH17 cell responses result in immune disorders including inflammatory bowel diseases. Interleukin (IL)-17-producing CD4+ T lymphocytes (TH17 cells) constitute a subset of T-helper cells involved in host defence and several immune disorders1,2. An intriguing feature of TH17 cells is their selective and constitutive presence in the intestinal Lamina Propria3. Here we show that adenosine 5′-triphosphate (ATP) that can be derived from commensal bacteria activates a unique subset of Lamina Propria cells, CD70highCD11clow cells, leading to the differentiation of TH17 cells. Germ-free mice exhibit much lower concentrations of luminal ATP, accompanied by fewer Lamina Propria TH17 cells, compared to specific-pathogen-free mice. Systemic or rectal administration of ATP into these germ-free mice results in a marked increase in the number of Lamina Propria TH17 cells. A CD70highCD11clow subset of the Lamina Propria cells expresses TH17-prone molecules, such as IL-6, IL-23p19 and transforming-growth-factor-β-activating integrin-αV and -β8, in response to ATP stimulation, and preferentially induces TH17 differentiation of co-cultured naive CD4+ T cells. The critical role of ATP is further underscored by the observation that administration of ATP exacerbates a T-cell-mediated colitis model with enhanced TH17 differentiation. These observations highlight the importance of commensal bacteria and ATP for TH17 differentiation in health and disease, and offer an explanation of why TH17 cells specifically present in the intestinal Lamina Propria.
Michael J Bertovich - One of the best experts on this subject based on the ideXlab platform.
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increased activation of isolated intestinal Lamina Propria mononuclear cells in inflammatory bowel disease
Gastroenterology, 1991Co-Authors: Stefan Schreiber, Richard P Macdermott, Andreas Raedler, Ralf Pinnau, Michael J BertovichAbstract:Normal human Lamina Propria lymphocytes are in a heightened state of activation compared with peripheral blood with regard to cell-surface activation antigen expression (transferrin receptor, interleukin-2 receptor, 4F2) and the increased spontaneous secretion of immunoglobulins in vitro. This study evaluates the cell-surface expression of activation-associated antigens in different subpopulations of isolated colonic Lamina Propria mononuclear cells in inflammatory bowel disease. In pilot studies using three-color flow cytometry, autofluorescence was observed that was emitted by unstained Lamina Propria mononuclear cells, which interfered with both the sensitivity and the specificity of the analyses. Because a major portion of the intestinal lymphocyte populations of interest were autofluorescent, a method to remove autofluorescence signals was developed by designing a computer program for the subtraction of autofluorescence from the emissions of each individual cell. This technique increases both the sensitivity and specificity of flow-cytometric analyses of intestinal Lamina Propria mononuclear cells. Using fluorescence-activated cell-sorter analyses with subtraction of autofluorescence on a single-cell basis, increased expression of lymphocyte activation antigens (interleukin-2 receptor, transferrin receptor, 4F2) was found on the cell surface of isolated intestinal B cells, T cells, CD4+ T cells, and CD8+ T cells in both Crohn's disease and ulcerative colitis. Therefore, markedly increased intestinal lymphocyte activation is a major immunological alteration in inflammatory bowel disease and includes all lymphocyte subpopulations investigated in this study. In addition, 5-aminosalicylic acid, which is used for the treatment of intestinal inflammation in inflammatory bowel disease, inhibits the expression of cell-surface activation antigens on mitogen-activated peripheral blood lymphocytes in a dose-dependent manner. These observations suggest that lymphocyte activation may play an important role in underlying immune processes that lead to chronicity and perpetuation of inflammatory bowel disease and may implicate an additional mechanism for the therapeutic action of 5-aminosalicylic acid.
Bali Pulendran - One of the best experts on this subject based on the ideXlab platform.
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Lamina Propria macrophages and dendritic cells differentially induce regulatory and interleukin 17 producing t cell responses
Nature Immunology, 2007Co-Authors: Timothy L Denning, Yi Chong Wang, Ifor R. Williams, Seema R. Patel, Bali PulendranAbstract:Lamina Propria macrophages and dendritic cells differentially induce regulatory and interleukin 17–producing T cell responses
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Lamina Propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses
Nature Immunology, 2007Co-Authors: Timothy L Denning, Yi Chong Wang, Ifor R. Williams, Seema R. Patel, Bali PulendranAbstract:The intestinal immune system must elicit robust immunity against harmful pathogens but must also restrain immune responses directed against commensal microbes and dietary antigens. The mechanisms that maintain this dichotomy are poorly understood. Here we describe a population of CD11b+F4/80+CD11c- macrophages in the Lamina Propria that expressed several anti-inflammatory molecules, including interleukin 10 (IL-10), but little or no proinflammatory cytokines, even after stimulation with Toll-like receptor ligands. These macrophages induced, by a mechanism dependent on IL-10, retinoic acid and exogenous transforming growth factor-beta, the differentiation of Foxp3+ regulatory T cells. In contrast, Lamina Propria CD11b+ dendritic cells elicited IL-17 production. This IL-17 production was suppressed by Lamina Propria macrophages, indicating that a dynamic interaction between these subsets may influence the balance between immune activation and tolerance.
Alexandra Valloneberhard - One of the best experts on this subject based on the ideXlab platform.
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transepithelial pathogen uptake into the small intestinal Lamina Propria
Journal of Immunology, 2006Co-Authors: Alexandra Valloneberhard, Limor Landsman, Nir Yogev, Bernard Verrier, Steffen JungAbstract:The Lamina Propria that underlies and stabilizes the gut lining epithelium is densely populated with strategically located mononuclear phagocytes. Collectively, these Lamina Propria macrophages and dendritic cells (DC) are believed to be crucial for tissue homeostasis as well as the innate and adaptive host defense. Lamina Propria DC were recently shown to gain direct access to the intestinal lumen by virtue of epithelium-penetrating dendrites. However, the role of these structures in pathogen uptake remains under debate. In this study, we report that entry of a noninvasive model pathogen (Aspergillus fumigatus conidia) into the murine small intestinal Lamina Propria persists in the absence of either transepithelial dendrites or Lamina Propria DC and macrophages. Our results suggest the existence of multiple pathogen entry pathways and point at the importance of villus M cells in the uptake of gut lumen Ags. Interestingly, transepithelial dendrites seem altogether absent from the small intestine of BALB/c mice suggesting that the function of Lamina Propria DC extensions resides in their potential selectivity for luminal Ags, rather than in general uptake or gut homeostasis.
