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Find video protocols related to scientific articles indexed in Pubmed.
Caspase-8 controls the gut response to microbial challenges by Tnf-?-dependent and independent pathways.
Gut
PUBLISHED: 11-08-2014
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Intestinal epithelial cells (IEC) express toll-like receptors (TLR) that facilitate microbial recognition. Stimulation of TLR ligands induces a transient increase in epithelial cell shedding, a mechanism that serves the antibacterial and antiviral host defence of the epithelium and promotes elimination of intracellular pathogens. Although activation of the extrinsic apoptosis pathway has been described during inflammatory shedding, its functional involvement is currently unclear.
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Accumulation and therapeutic modulation of 6-sulfo LacNAc(+) dendritic cells in multiple sclerosis.
Neurol Neuroimmunol Neuroinflamm
PUBLISHED: 10-01-2014
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To examine the potential role of 6-sulfo LacNAc(+) (slan) dendritic cells (DCs) displaying pronounced proinflammatory properties in the pathogenesis of multiple sclerosis (MS).
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Murine CD83-positive T cells mediate suppressor functions in vitro and in vivo.
Immunobiology
PUBLISHED: 08-10-2014
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The CD83 molecule (CD83) is a well-known surface marker present on mature dendritic cells (mDC). In this study, we show that CD83 is also expressed on a subset of T cells which mediate regulatory T cell (Treg)-like suppressor functions in vitro and in vivo. Treg-associated molecules including CD25, cytotoxic T lymphocyte antigen-4 (CTLA-4), glucocorticoid-induced TNFR family-related gene (GITR), Helios and neuropilin-1 (NRP-1) as well as forkhead box protein 3 (FOXP3) were specifically expressed by these CD83(+) T cells. In contrast, CD83(-) T cells showed a naive T cell phenotype with effector T cell properties upon activation. Noteworthy, CD83(-) T cells were not able to upregulate CD83 despite activation. Furthermore, CD83(+) T cells suppressed the proliferation and inflammatory cytokine release of CD83(-) T cells in vitro. Strikingly, stimulated CD83(+) T cells released soluble CD83 (sCD83), which has been reported to possess immunosuppressive properties. In vivo, using the murine transfer colitis model we could show that CD83(+) T cells were able to suppress colitis symptoms while CD83(-) T cells possessed effector functions. In addition, this CD83 expression is also conserved on expanded human Treg. Thus, from these studies we conclude that CD83(+) T cells share important features with regulatory T cells, identifying CD83 as a novel lineage marker to discriminate between different T cell populations.
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Esophageal epithelial resistance.
Dig Dis
PUBLISHED: 02-28-2014
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Besides its important role of digestion and absorption, esophageal tissue has an essential role as a major barrier against intraluminal pathogens like hostile microorganisms and toxins. This barrier function is achieved via various mechanical, chemical, and immunological mechanisms which are typically altered in inflammatory diseases, thereby causing subsequent damage of the mucosa. In this review we will focus on the main structural and functional barriers of host defense within the esophageal mucosa, including the epithelial layer, membrane-bound and secretory mucins, and different types of defensins. In addition, we will discuss the relevance of biofilm on esophageal tissue and will illustrate the importance of different regulators of intestinal permeability like zonulin and desmosomal components.
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Regulation and pathophysiological role of epithelial turnover in the gut.
Semin. Cell Dev. Biol.
PUBLISHED: 02-27-2014
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Cell death in the intestinal epithelium has to be tightly controlled. Excessive or misplaced epithelial cell death can result in barrier dysfunction and, as a consequence thereof, uncontrolled translocation of components of the microbial flora from the lumen into the bowel wall. Susceptibility to gastrointestinal infections or chronic inflammation of the gut, as observed in patients with inflammatory bowel disease, can be the result of such dysregulation. Conversely, defects in cell death initiation might lead to an irregular accumulation of epithelial cells and cause intestinal cancer development. Until recently, activation of caspases in the intestinal epithelium was considered as a potential contributor to barrier dysfunction and as a pathogenic factor in the development of intestinal inflammation. Thus blocking of caspases appeared to be a potential therapeutic option for patients with inflammatory bowel disease. Recent studies on necroptosis however demonstrated that also inhibition of caspases can cause barrier dysfunction and intestinal inflammation. Caspase-8 on top of its functions in the extrinsic apoptosis pathway also controls necroptosis and turns out to be an essential molecule in regulating tissue homeostasis in the gut. Epithelial caspase-8 therefore emerges as a checkpoint not only of cell survival and cell death, but also as a regulator of the mode of cell death. According to this model, both excessive activity as well as a lack of activity of caspase-8 results in epithelial cell death and intestinal inflammation and caspase-8 needs to be tightly controlled to warrant tissue homeostasis in the gut.
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RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis.
Nature
PUBLISHED: 02-16-2014
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Receptor interacting protein kinase 1 (RIPK1) has an essential role in the signalling triggered by death receptors and pattern recognition receptors. RIPK1 is believed to function as a node driving NF-?B-mediated cell survival and inflammation as well as caspase-8 (CASP8)-dependent apoptotic or RIPK3/MLKL-dependent necroptotic cell death. The physiological relevance of this dual function has remained elusive because of the perinatal death of RIPK1 full knockout mice. To circumvent this problem, we generated RIPK1 conditional knockout mice, and show that mice lacking RIPK1 in intestinal epithelial cells (IECs) spontaneously develop severe intestinal inflammation associated with IEC apoptosis leading to early death. This early lethality was rescued by antibiotic treatment, MYD88 deficiency or tumour-necrosis factor (TNF) receptor 1 deficiency, demonstrating the importance of commensal bacteria and TNF in the IEC Ripk1 knockout phenotype. CASP8 deficiency, but not RIPK3 deficiency, rescued the inflammatory phenotype completely, indicating the indispensable role of RIPK1 in suppressing CASP8-dependent apoptosis but not RIPK3-dependent necroptosis in the intestine. RIPK1 kinase-dead knock-in mice did not exhibit any sign of inflammation, suggesting that RIPK1-mediated protection resides in its kinase-independent platform function. Depletion of RIPK1 in intestinal organoid cultures sensitized them to TNF-induced apoptosis, confirming the in vivo observations. Unexpectedly, TNF-mediated NF-?B activation remained intact in these organoids. Our results demonstrate that RIPK1 is essential for survival of IECs, ensuring epithelial homeostasis by protecting the epithelium from CASP8-mediated IEC apoptosis independently of its kinase activity and NF-?B activation.
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Norovirus triggered microbiota-driven mucosal inflammation in interleukin 10-deficient mice.
Inflamm. Bowel Dis.
PUBLISHED: 02-04-2014
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Infection may trigger clinically overt mucosal inflammation in patients with predisposition for inflammatory bowel disease. However, the impact of particular enteropathogenic microorganisms is ill-defined. In this study, the influence of murine norovirus (MNV) infection on clinical, histopathological, and immunological features of mucosal inflammation in the IL10-deficient (Il10) mouse model of inflammatory bowel disease was examined.
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Cellular FLICE-Like Inhibitory Protein Secures Intestinal Epithelial Cell Survival and Immune Homeostasis by Regulating Caspase-8.
Gastroenterology
PUBLISHED: 08-01-2013
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The intestinal epithelium generates a barrier that protects mammals from potentially harmful intestinal contents, such as pathogenic bacteria. Dysregulation of epithelial cell death has been implicated in barrier dysfunction and in the pathogenesis of intestinal inflammation. We investigated mechanisms of cell-death regulation in the intestinal epithelium of mice.
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Virtual chromoendoscopy for prediction of severity and disease extent in patients with inflammatory bowel disease: a randomized controlled study.
Inflamm. Bowel Dis.
PUBLISHED: 07-11-2013
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Increased vascular permeability and angiogenesis play a crucial role in the pathogenesis of inflammatory bowel disease (IBD). Aim was to determine whether computed virtual chromoendoscopy has the potential to enhance assessment of disease severity and extent in patients with mild or inactive IBD in comparison to high-definition white-light endoscopy.
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Reduction of inflammatory slan (6-sulfo LacNAc) dendritic cells in psoriatic skin of patients treated with etanercept.
Exp. Dermatol.
PUBLISHED: 06-11-2013
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Dermal dendritic cells (DCs) play a central role in the immunopathology of psoriasis. We previously identified slanDCs as pro-inflammatory TNF-?, IL-23- and IL-12-producing DCs in human blood and as prominent inflammatory dermal TNF-? secreting and CD11c-positive DC subset in psoriasis. Here, we ask for the effects of TNF-?-inhibition on inflammatory slanDCs in skin and blood of 10 patients with psoriasis during 24 weeks of treatment with etanercept. Treatment with etanercept reduced the frequency of dermal slanDCs but did not induce apoptosis as determined by lack of increased active caspase-3-expression. In parallel, we found increased frequencies of slanDCs in blood which expressed lower levels of HLA-DR. Stimulating slanDCs isolated from the blood of healthy donors in vitro induced a strong production of IL-1?, IL-6, IL-23 and IL-12p70. This capacity was efficiently reduced in the presence of etanercept, thereby indicating that TNF-? is an autocrine stimulus for maturation and pro-inflammatory cytokine production of slanDCs. In vivo, we noticed that treatment with etanercept did reduce the number of dermal slanDCs in parallel to the overall expression of TNF-? and IL-23p19. However, successful treatment did not down-regulated the percentage of dermal slanDCs that stained positive for TNF-? and IL-23p19 indicating that remaining slanDCs kept their pro-inflammatory capacity. This study provides novel insights into the immune regulatory properties of etanercept at the level of inflammatory slanDCs in vivo in skin and blood as well as in vitro.
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Confocal laser endomicroscopy for in vivo diagnosis of Clostridium difficile associated colitis - a pilot study.
PLoS ONE
PUBLISHED: 02-06-2013
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Clostridium difficile infection (CDI) is one of the most dreaded causes of hospital-acquired diarrhea. Main objective was to investigate whether confocal laser endomicroscopy (CLE) has the capability for in vivo diagnosis of C. difficile associated histological changes. Second objective was to prove the presence of intramucosal bacteria using CLE.
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Learning curve of virtual chromoendoscopy for the prediction of hyperplastic and adenomatous colorectal lesions: a prospective 2-center study.
Gastrointest. Endosc.
PUBLISHED: 02-01-2013
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Computed virtual chromoendoscopy (CVC) enables high-definition imaging of mucosal lesions with improved tissue contrast. Previous studies have shown that CVC yields an improved detection rate of colorectal lesions. However, the learning curve for interpretation of CVC images is unknown.
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CXCL16 and CXCR6 are upregulated in psoriasis and mediate cutaneous recruitment of human CD8+ T cells.
J. Invest. Dermatol.
PUBLISHED: 11-24-2011
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Psoriatic skin lesions are characterized by an inflammatory infiltrate, consisting of dendritic cells, monocytes, and both CD4(+) and CD8(+) T lymphocytes. Although the chemokines involved in the migration of CD4(+) T cells into psoriatic skin are well characterized, those regulating CD8(+) T-cell recruitment are less understood. We found that the percentages of peripheral blood CD8(+) T cells expressing CXCR6 were higher in psoriatic patients than in healthy or atopic individuals. In addition, CXCR6 expression in psoriatic patients was more abundant in the CD8(+) than in the CD4(+) T-cell compartment. CXCR6 mRNA expression was also stronger in skin CD8(+) T cells than in the corresponding blood-derived counterparts. Immunofluorescence analysis revealed profound upregulation of the CXCR6 ligand CXCL16 by monocytes, keratinocytes, and dendritic cells in psoriatic skin compared with healthy or atopic dermatitis skin. In line with this, CXCR6(+) CD8(+) T cells also were most prevalent in psoriatic skin. Furthermore, CXCL16 induced Ca(2+) influx and chemotactic migration of psoriatic skin-derived CD8(+) T cells in vitro. Most importantly, CXCL16 potently recruited human CD8(+) T cells to human skin grafts previously transplanted onto SCID mice in vivo. These investigations indicate that CXCL16-CXCR6 interactions mediate homing of CD8(+) T cells into human skin, and thereby contribute to psoriasis pathogenesis.
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Advanced endoscopic imaging for diagnosis of Crohns disease.
Gastroenterol Res Pract
PUBLISHED: 08-29-2011
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Endoscopy in IBD has tremendous importance to diagnose inflammatory activity, to evaluate therapeutic success and for the surveillance of colitis associated cancer. Thus it becomes obvious that there is a need for new and more advanced endoscopic imaging techniques for better characterization of mucosal inflammation and early neoplasia detection in IBD. This paper describes the concept of advanced endoscopic imaging for the diagnosis and characterization of Crohns disease, including magnification endoscopy, chromoendoscopy, balloon-assisted enteroscopy, capsule endoscopy, confocal laser endomicroscopy, and endocytoscopy.
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Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong TH17/TH1 T-cell responses.
J. Allergy Clin. Immunol.
PUBLISHED: 03-08-2011
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Psoriasis is a chronic inflammatory skin disease that is considered to result from activated T cells stimulated by a population of inflammatory dermal dendritic cells (DCs). The origin and identity of these inflammatory dermal DCs are largely unknown.
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Caspase-8 regulates TNF-?-induced epithelial necroptosis and terminal ileitis.
Nature
PUBLISHED: 02-02-2011
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Dysfunction of the intestinal epithelium is believed to result in the excessive translocation of commensal bacteria into the bowel wall that drives chronic mucosal inflammation in Crohns disease, an incurable inflammatory bowel disease in humans characterized by inflammation of the terminal ileum. In healthy individuals, the intestinal epithelium maintains a physical barrier, established by the tight contact of cells. Moreover, specialized epithelial cells such as Paneth cells and goblet cells provide innate immune defence functions by secreting mucus and antimicrobial peptides, which hamper access and survival of bacteria adjacent to the epithelium. Epithelial cell death is a hallmark of intestinal inflammation and has been discussed as a possible pathogenic mechanism driving Crohns disease in humans. However, the regulation of epithelial cell death and its role in intestinal homeostasis remain poorly understood. Here we demonstrate a critical role for caspase-8 in regulating necroptosis of intestinal epithelial cells (IECs) and terminal ileitis. Mice with a conditional deletion of caspase-8 in the intestinal epithelium (Casp8(?IEC)) spontaneously developed inflammatory lesions in the terminal ileum and were highly susceptible to colitis. Casp8(?IEC) mice lacked Paneth cells and showed reduced numbers of goblet cells, indicating dysregulated antimicrobial immune cell functions of the intestinal epithelium. Casp8(?IEC) mice showed increased cell death in the Paneth cell area of small intestinal crypts. Epithelial cell death was induced by tumour necrosis factor (TNF)-?, was associated with increased expression of receptor-interacting protein 3 (Rip3; also known as Ripk3) and could be inhibited on blockade of necroptosis. Lastly, we identified high levels of RIP3 in human Paneth cells and increased necroptosis in the terminal ileum of patients with Crohns disease, suggesting a potential role of necroptosis in the pathogenesis of this disease. Together, our data demonstrate a critical function of caspase-8 in regulating intestinal homeostasis and in protecting IECs from TNF-?-induced necroptotic cell death.
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Up-regulation of the chemokine CCL18 by macrophages is a potential immunomodulatory pathway in cutaneous T-cell lymphoma.
Am. J. Pathol.
PUBLISHED: 01-06-2011
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Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma (CTCL), which can deteriorate from patch stage to dermal-based tumors and systemic involvement in years. The interaction of chemokines in the skin with CTCL cells might have implications for the pathogenesis of the disease. In this study, we show by PCR analysis and immunofluorescence staining that the chemokine CCL18 is present in skin biopsy specimens of patients with MF and its precursor form parapsoriasis en plaque but not in healthy tissue. In addition, the serum levels of CCL18 were increased threefold in MF patients compared with those in healthy controls. In skin, CCL18 was specifically expressed by CD163(+) CD209(+) macrophages at the invasive margin of the tumor and not expressed by mature CD208(+) dendritic cells in the center of the tumor. The chemokine CCL17 was, by contrast, ubiquitously expressed. Furthermore, CCL18 promoted the chemotaxis but not the proliferation of CTCL cells. CCL18 inhibited proliferation of tumor cells and abolished the CXCL12-induced growth of a CTCL cell line. These data link the increased expression of CCL18 with CTCL and suggest an immunomodulatory effect of the chemokine in the pathogenesis of CTCL.
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Assessment of tumor development and wound healing using endoscopic techniques in mice.
Gastroenterology
PUBLISHED: 10-16-2010
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Mouse models of intestinal inflammation and colon cancer are valuable tools to gain insights into the pathogenesis of the corresponding human diseases. Recently, in vivo mouse endoscopy has been developed, allowing not only the high-resolution monitoring and scoring of experimental disease development, but also enables the investigator to perform manipulations, including local injection of reagents or the taking of biopsies for molecular and histopathologic analyses. Chromoendoscopic staining with methylene blue enables visualization of the crypt structure and allows discrimination between inflammatory and neoplastic changes. The development of endoscopic techniques in live mice opened new options for the investigation of disease mechanisms in the gut and for the preclinical testing of potential therapeutic effects of drug candidates. Finally, mouse endoscopy can help to reduce animal numbers needed to gain significant experimental data.
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Localized morphea--a rare but significant secondary complication following breast cancer radiotherapy. Case report and review of the literature on radiation reaction among patients with scleroderma/morphea.
Strahlenther Onkol
PUBLISHED: 05-06-2009
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PURPOSE AND APPROACH: To report a case of morphea (localized scleroderma) in a patient following breast cancer therapy and to summarize the current literature.
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Innate immune processes in lupus erythematosus.
Clin. Immunol.
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The innate immune system is involved in the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE) or dermatomyositis. The important role of complement factors of the classical pathway and of Toll like receptors (TLRs) is well established, based on genetic and clinical evidence. Immune complexes activate tumor necrosis factor (TNF) in myeloid cells and interferon-? (IFN?) in plasmacytoid dendritic cells. The latter initiates a positive feedback loop that drives autoimmunity. More recently, mutations in genes encoding intracellular enzymes involved in RNA and DNA handling, which likewise lead to increased IFN?, have been found to cause familial chilblain lupus and to be associated with SLE. Within the immunological disease continuum, these disorders can be placed between autoinflammation and autoimmunity, and we would propose the term autoadjuvant for this group, since the activation of the innate immune system in these diseases appears to lower the threshold for (auto)immune reactions.
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Human 6-sulfo LacNAc (slan) dendritic cells have molecular and functional features of an important pro-inflammatory cell type in lupus erythematosus.
J. Autoimmun.
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Lupus erythematosus (LE) is an autoimmune disease with evidence for an IL-23- and IL-17-induced immunopathology. Little is known about the type of dendritic cells supporting this immune response. We recently demonstrated the strong Th1- and Th17-T-cell inducing capacity of human 6-sulfo LacNAc-dendritic cells (slanDCs), and identified slanDCs as inflammatory dermal dendritic cells in psoriasis locally expressing IL-23, TNF-? and inducible nitric oxide synthase (iNOS). In this study, we investigated the role of slanDCs in LE. Using immunohistochemistry, we identified slanDCs at increased frequency in affected skin lesions of cutaneous and systemic LE. slanDCs were found scattered in the dermal compartment and also clustered in lymph follicle-like structures. Here, they colocalized with T cells in the periphery but not with B cells in the center. The positive staining of dermal slanDCs for TNF-? indicated their pro-inflammatory status. In vitro the production of TNF-? was induced when slanDCs were cultured in the presence of serum from patients with LE. Stimulatory components of LE serum were previously identified as autoimmune complexes with ssRNA binding to TLR7 and TLR8. We found that slanDCs express mRNA for TLR7 and TLR8. slanDCs stimulated with ssRNA, selective TLR7 or TLR8 ligands responded with high-level TNF-? and IL-12 production. In contrast to slanDCs, the population of CD1c(+) DCs and plasmacytoid DCs (pDCs) expressed either TLR7 or TLR8, and their production of TNF-? and IL-12 to respective ligands was far less pronounced. We conclude that slanDCs have molecular and functional features of a pro-inflammatory myeloid DC type relevant for the immunopathogenesis of LE.
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Treatment satisfaction and health status in patients with systemic sclerosis.
J Dtsch Dermatol Ges
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Systemic sclerosis (SSc) is a rare connective tissue disease. Few data are available on treatment satisfaction, determinants of quality of life, and the health status of dermatology patients with SSc.
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Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium.
Gut
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Intestinal epithelial cells (IEC) are organised as a single cell layer which covers the intestine. Their primary task is to absorb nutrients present in the intestinal lumen. However, IEC also play an important role in the immune defence of our body by building a barrier that separates the bowel wall from potentially hazardous bacteria present in the gut lumen. The life cycle of IEC is determined by the time span in which cells migrate from their place of origin at the crypt base to the villus tip, from where they are shed into the lumen. Cell death in the intestinal epithelium has to be tightly regulated and irregularities might cause pathologies. Excessive cell death has been associated with chronic inflammation as seen in patients with Crohns disease and ulcerative colitis. While until recently apoptosis was discussed as being essential for epithelial turnover and tissue homeostasis in the intestinal epithelium, recent data using gene deficient mice have challenged this concept. Moreover, an apoptosis-independent mode of programmed cell death, termed necroptosis, has been identified and described in the intestinal epithelium. The following article reviews previous studies on cell death regulation in IEC and a potential role of necroptosis for gut homeostasis.
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Lack of intestinal epithelial atg7 affects paneth cell granule formation but does not compromise immune homeostasis in the gut.
Clin. Dev. Immunol.
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Genetic polymorphisms of autophagy-related genes have been associated with an increased risk to develop inflammatory bowel disease (IBD). Autophagy is an elementary process participating in several cellular events such as cellular clearance and nonapoptotic programmed cell death. Furthermore, autophagy may be involved in intestinal immune homeostasis due to its participation in the digestion of intracellular pathogens and in antigen presentation. In the present study, the role of autophagy in the intestinal epithelial layer was investigated. The intestinal epithelium is essential to maintain gut homeostasis, and defects within this barrier have been associated with the pathogenesis of IBD. Therefore, mice with intestinal epithelial deletion of Atg7 were generated and investigated in different mouse models. Knockout mice showed reduced size of granules and decreased levels of lysozyme in Paneth cells. However, this was dispensable for gut immune homeostasis and had no effect on susceptibility in mouse models of experimentally induced colitis.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.