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Immunological Reviews Sep 2021Most antibodies produced in the body are of the IgA class. The dominant cell population producing them are plasma cells within the lamina propria of the gastrointestinal... (Review)
Review
Most antibodies produced in the body are of the IgA class. The dominant cell population producing them are plasma cells within the lamina propria of the gastrointestinal tract, but many IgA-producing cells are also found in the airways, within mammary tissues, the urogenital tract and inside the bone marrow. Most IgA antibodies are transported into the lumen by epithelial cells as part of the mucosal secretions, but they are also present in serum and other body fluids. A large part of the commensal microbiota in the gut is covered with IgA antibodies, and it has been demonstrated that this plays a role in maintaining a healthy balance between the host and the bacteria. However, IgA antibodies also play important roles in neutralizing pathogens in the gastrointestinal tract and the upper airways. The distinction between the two roles of IgA - protective and balance-maintaining - not only has implications on function but also on how the production is regulated. Here, we discuss these issues with a special focus on gut and airways.
Topics: Friends; Humans; Immunity, Mucosal; Immunoglobulin A; Intestinal Mucosa; Mucous Membrane; Plasma Cells
PubMed: 34331314
DOI: 10.1111/imr.13014 -
Tissue Engineering and Regenerative... Oct 2021Vaccination has been recently attracted as one of the most successful medical treatments of the prevalence of many infectious diseases. Mucosal vaccination has been... (Review)
Review
Vaccination has been recently attracted as one of the most successful medical treatments of the prevalence of many infectious diseases. Mucosal vaccination has been interested in many researchers because mucosal immune responses play part in the first line of defense against pathogens. However, mucosal vaccination should find out an efficient antigen delivery system because the antigen should be protected from degradation and clearance, it should be targeted to mucosal sites, and it should stimulate mucosal and systemic immunity. Accordingly, mucoadhesive polymeric particles among the polymeric particles have gained much attention because they can protect the antigen from degradation, prolong the residence time of the antigen at the target site, and control the release of the loaded vaccine, and results in induction of mucosal and systemic immune responses. In this review, we discuss advances in the development of several kinds of mucoadhesive polymeric particles for mucosal vaccine delivery.
Topics: Drug Delivery Systems; Immunity, Mucosal; Mucous Membrane; Polymers; Vaccines
PubMed: 34304387
DOI: 10.1007/s13770-021-00373-w -
Biomedicine & Pharmacotherapy =... May 2023Nanodrug delivery systems have been widely used in disease treatment. However, weak drug targeting, easy to be cleared by the immune system, and low biocompatibility are... (Review)
Review
Nanodrug delivery systems have been widely used in disease treatment. However, weak drug targeting, easy to be cleared by the immune system, and low biocompatibility are great obstacles for drug delivery. As an important part of cell information transmission and behavior regulation, cell membrane can be used as drug coating material which represents a promising strategy and can overcome these limitations. Mesenchymal stem cell (MSC) membrane, as a new carrier, has the characteristics of active targeting and immune escape of MSC, and has broad application potential in tumor treatment, inflammatory disease, tissue regeneration and other fields. Here, we review recent progress on the use of MSC membrane-coated nanoparticles for therapy and drug delivery, aiming to provide guidance for the design and clinical application of membrane carrier in the future.
Topics: Membranes; Drug Delivery Systems; Cell Membrane; Nanoparticles; Mesenchymal Stem Cells; Excipients
PubMed: 36870279
DOI: 10.1016/j.biopha.2023.114451 -
Frontiers in Immunology 2021Type 3 Innate lymphoid cells (ILC3s) have been described as tissue-resident cells and characterized throughout the body, especially in mucosal sites and classical first... (Review)
Review
Type 3 Innate lymphoid cells (ILC3s) have been described as tissue-resident cells and characterized throughout the body, especially in mucosal sites and classical first barrier organs such as skin, gut and lungs, among others. A significant part of the research has focused on their role in combating pathogens, mainly extracellular pathogens, with the gut as the principal organ. However, some recent discoveries in the field have unveiled their activity in other organs, combating intracellular pathogens and as part of the response to viruses. In this review we have compiled the latest studies on the role of ILC3s and the molecular mechanisms involved in defending against different microbes at the mucosal surface, most of these studies have made use of conditional transgenic mice. The present review therefore attempts to provide an overview of the function of ILC3s in infections throughout the body, focusing on their specific activity in different organs.
Topics: Animals; Gastrointestinal Tract; Host-Pathogen Interactions; Humans; Immunity, Innate; Infections; Lung; Lymphocytes; Mouth Mucosa; Skin
PubMed: 34659248
DOI: 10.3389/fimmu.2021.748851 -
Italian Journal of Dermatology and... Oct 2023The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of... (Review)
Review
The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of these conditions are immune mediated and typically present as inflammatory mucosal pathology. Patients experiencing such conditions usually seek medical evaluation and treatment due to the associated pain and discomfort and occasionally taste disturbance or dysphagia and the overall deterioration in the oral health-related quality of life. These conditions share some common features and there could be some overlapping in their clinical presentation, which can lead to delays in diagnosis and proper management of patients. Clinicians dealing with such disorders, including dermatologists, need to be aware of the oral manifestations of mucocutaneous conditions, their clinical features, underlying mechanisms, diagnostic approaches, and treatment options, as well as the recent advances in the research on these conditions. This review provides a comprehensive, evidence-based reference for clinicians, with updated insights into a group of immune mediated conditions known to cause oral mucosal pathology. Part one will cover oral lichen planus, erythema multiforme and systemic lupus erythematosus, while part two will cover pemphigus vulgaris and mucous membrane pemphigoid, recurrent aphthous stomatitis, in addition to the less common disorders linear IgA disease, dermatitis herpetiformis and epidermolysis bullosa.
Topics: Humans; Mouth Mucosa; Mouth Diseases; Quality of Life; Stomatitis, Aphthous; Pemphigus
PubMed: 37916401
DOI: 10.23736/S2784-8671.23.07676-4 -
Nature Cancer Feb 2024Metastatic gastric carcinoma is a highly lethal cancer that responds poorly to conventional and molecularly targeted therapies. Despite its clinical relevance, the...
Metastatic gastric carcinoma is a highly lethal cancer that responds poorly to conventional and molecularly targeted therapies. Despite its clinical relevance, the mechanisms underlying the behavior and therapeutic response of this disease are poorly understood owing, in part, to a paucity of tractable models. Here we developed methods to somatically introduce different oncogenic lesions directly into the murine gastric epithelium. Genotypic configurations observed in patients produced metastatic gastric cancers that recapitulated the histological, molecular and clinical features of all nonviral molecular subtypes of the human disease. Applying this platform to both wild-type and immunodeficient mice revealed previously unappreciated links between the genotype, organotropism and immune surveillance of metastatic cells, which produced distinct patterns of metastasis that were mirrored in patients. Our results establish a highly portable platform for generating autochthonous cancer models with flexible genotypes and host backgrounds, which can unravel mechanisms of gastric tumorigenesis or test new therapeutic concepts.
Topics: Humans; Mice; Animals; Stomach Neoplasms; Disease Models, Animal; Gastric Mucosa; Genotype
PubMed: 38177458
DOI: 10.1038/s43018-023-00686-w -
Proceedings of the National Academy of... Feb 2023Lysosomal exocytosis is involved in many key cellular processes but its spatiotemporal regulation is poorly known. Using total internal reflection fluorescence...
Lysosomal exocytosis is involved in many key cellular processes but its spatiotemporal regulation is poorly known. Using total internal reflection fluorescence microscopy (TIRFM) and spatial statistics, we observed that lysosomal exocytosis is not random at the adhesive part of the plasma membrane of RPE1 cells but clustered at different scales. Although the rate of exocytosis is regulated by the actin cytoskeleton, neither interfering with actin or microtubule dynamics by drug treatments alters its spatial organization. Exocytosis events partially co-appear at focal adhesions (FAs) and their clustering is reduced upon removal of FAs. Changes in membrane tension following a hypo-osmotic shock or treatment with methyl-β-cyclodextrin were found to increase clustering. To investigate the link between FAs and membrane tension, cells were cultured on adhesive ring-shaped micropatterns, which allow to control the spatial organization of FAs. By using a combination of TIRFM and fluorescence lifetime imaging microscopy (FLIM), we revealed the existence of a radial gradient in membrane tension. By changing the diameter of micropatterned substrates, we further showed that this gradient as well as the extent of exocytosis clustering can be controlled. Together, our data indicate that the spatial clustering of lysosomal exocytosis relies on membrane tension patterning controlled by the spatial organization of FAs.
Topics: Cell Membrane; Exocytosis; Membranes; Cell Physiological Phenomena; Lysosomes
PubMed: 36800388
DOI: 10.1073/pnas.2207425120 -
Biochemical Society Transactions Oct 2022The mucus layer covering the gastrointestinal (GI) tract plays a critical role in maintaining gut homeostasis. In the colon, the inner mucus layer ensures commensal... (Review)
Review
The mucus layer covering the gastrointestinal (GI) tract plays a critical role in maintaining gut homeostasis. In the colon, the inner mucus layer ensures commensal microbes are kept at a safe distance from the epithelium while mucin glycans in the outer mucus layer provide microbes with nutrients and binding sites. Microbes residing in the mucus form part of the so-called 'mucosa-associated microbiota' (MAM), a microbial community which, due to its close proximity to the epithelium, has a profound impact on immune and metabolic health by directly impacting gut barrier function and the immune system. Alterations in GI microbial communities have been linked to human diseases. Although most of this knowledge is based on analysis of the faecal microbiota, a growing number of studies show that the MAM signature differs from faecal or luminal microbiota and has the potential to be used to distinguish between diseased and healthy status in well-studied conditions such as IBD, IBS and CRC. However, our knowledge about spatial microbial alterations in pathogenesis remains severely hampered by issues surrounding access to microbial communities in the human gut. In this review, we provide state-of-the-art information on how to access MAM in humans, the composition of MAM, and how changes in MAM relate to changes in human health and disease. A better understanding of interactions occurring at the mucosal surface is essential to advance our understanding of diseases affecting the GI tract and beyond.
Topics: Humans; Gastrointestinal Microbiome; Intestinal Mucosa; Colon; Mucus; Microbiota
PubMed: 36214382
DOI: 10.1042/BST20201201 -
International Journal of Molecular... Nov 2019Epicardial adipose tissue (EAT) is part of the visceral adipose tissue (VAT) that surrounds the heart and it is a quantifiable, modifiable, and multifaceted tissue that... (Review)
Review
Epicardial adipose tissue (EAT) is part of the visceral adipose tissue (VAT) that surrounds the heart and it is a quantifiable, modifiable, and multifaceted tissue that has both local and systemic effects. When EAT is enlarged, EAT contributes to atherosclerotic cardiovascular disease (ASCVD) risk and plays a role in the development of metabolic syndrome (MetS). In this review, we will discuss the role of EAT in various facets of MetS, including type 2 diabetes mellitus (T2DM) and insulin resistance. We examine the association between EAT and liver steatosis. We also address the correlations of EAT with HIV therapy and with psoriasis. We discuss racial differences in baseline EAT thickness. We conclude that EAT measurement serves as a powerful potential diagnostic tool in assessing cardiovascular and metabolic risk. Measurement of EAT is made less costly, more convenient, and yet accurate and reliable by transthoracic echocardiography. Furthermore, modification of EAT thickness has therapeutic implications for ASCVD, T2DM, and MetS.
Topics: Biomarkers; Cardiovascular Diseases; Humans; Intra-Abdominal Fat; Lipid Metabolism; Metabolic Syndrome; Pericardium
PubMed: 31795098
DOI: 10.3390/ijms20235989 -
Communications Biology Aug 2021The position of abdominal organs, and mechanisms by which these are centrally connected, are currently described in peritoneal terms. As part of the peritoneal model of...
The position of abdominal organs, and mechanisms by which these are centrally connected, are currently described in peritoneal terms. As part of the peritoneal model of abdominal anatomy, there are multiple mesenteries. Recent findings point to an alternative model in which digestive organs are connected to a single mesentery. Given that direct evidence of this is currently lacking, we investigated the development and shape of the entire mesentery. Here we confirm that, within the abdomen, there is one mesentery in which all abdominal digestive organs develop and remain connected to. We show that all abdominopelvic organs are organised into two, discrete anatomical domains, the mesenteric and non-mesenteric domain. A similar organisation occurs across a range of animal species. The findings clarify the anatomical foundation of the abdomen; at the foundation level, the abdomen comprises a visceral (i.e. mesenteric) and somatic (i.e. musculoskeletal) frame. The organisation at that level is a fundamental order that explains the positional anatomy of all abdominopelvic organs, vasculature and peritoneum. Collectively, the findings provide a novel start point from which to systemically characterise the abdomen and its contents.
Topics: Humans; Mesentery; Peritoneum
PubMed: 34408242
DOI: 10.1038/s42003-021-02496-1