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Nature Reviews. Cancer Oct 2017Metaplasia is the replacement of one differentiated somatic cell type with another differentiated somatic cell type in the same tissue. Typically, metaplasia is... (Review)
Review
Metaplasia is the replacement of one differentiated somatic cell type with another differentiated somatic cell type in the same tissue. Typically, metaplasia is triggered by environmental stimuli, which may act in concert with the deleterious effects of microorganisms and inflammation. The cell of origin for intestinal metaplasia in the oesophagus and stomach and for pancreatic acinar-ductal metaplasia has been posited through genetic mouse models and lineage tracing but has not been identified in other types of metaplasia, such as squamous metaplasia. A hallmark of metaplasia is a change in cellular identity, and this process can be regulated by transcription factors that initiate and/or maintain cellular identity, perhaps in concert with epigenetic reprogramming. Universally, metaplasia is a precursor to low-grade dysplasia, which can culminate in high-grade dysplasia and carcinoma. Improved clinical screening for and surveillance of metaplasia might lead to better prevention or early detection of dysplasia and cancer.
Topics: Adaptation, Biological; Animals; Barrett Esophagus; Epigenesis, Genetic; Epithelium; Gastric Mucosa; Humans; Intestinal Mucosa; Metaplasia; Mucous Membrane; Respiratory Mucosa; Transcription Factors
PubMed: 28860646
DOI: 10.1038/nrc.2017.68 -
Immunological Reviews Jul 2014The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel-forming mucins... (Review)
Review
The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel-forming mucins MUC2 and MUC5AC are the major components of the mucus in the intestine and stomach, respectively. In the small intestine, mucus limits the number of bacteria that can reach the epithelium and the Peyer's patches. In the large intestine, the inner mucus layer separates the commensal bacteria from the host epithelium. The outer colonic mucus layer is the natural habitat for the commensal bacteria. The intestinal goblet cells secrete not only the MUC2 mucin but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and TFF3. The goblet cells have recently been shown to have a novel gate-keeping role for the presentation of oral antigens to the immune system. Goblet cells deliver small intestinal luminal material to the lamina propria dendritic cells of the tolerogenic CD103(+) type. In addition to the gel-forming mucins, the transmembrane mucins MUC3, MUC12, and MUC17 form the enterocyte glycocalyx that can reach about a micrometer out from the brush border. The MUC17 mucin can shuttle from a surface to an intracellular vesicle localization, suggesting that enterocytes might control and report epithelial microbial challenge. There is communication not only from the epithelial cells to the immune system but also in the opposite direction. One example of this is IL10 that can affect and improve the properties of the inner colonic mucus layer. The mucus and epithelial cells of the gastrointestinal tract are the primary gate keepers and controllers of bacterial interactions with the host immune system, but our understanding of this relationship is still in its infancy.
Topics: Animals; Enterocytes; Gastrointestinal Tract; Goblet Cells; Humans; Immune System; Mucins; Mucous Membrane; Mucus; Peyer's Patches
PubMed: 24942678
DOI: 10.1111/imr.12182 -
Frontiers in Immunology 2019Mucous membrane pemphigoid (MMP) is a mucous membrane-dominated autoimmune subepithelial blistering disease that is caused by autoantibodies against various autoantigens... (Review)
Review
Mucous membrane pemphigoid (MMP) is a mucous membrane-dominated autoimmune subepithelial blistering disease that is caused by autoantibodies against various autoantigens in basement membrane zone (BMZ) proteins, including collagen XVII (COL17). Clinicians face diagnostic problems in detecting circulating antibodies and targeted antigens in MMP. The diagnostic difficulties are mainly attributed to the low titers of MMP autoantibodies in sera and to heterogeneous autoantigens. Additionally, no unanimous diagnostic criteria have been drawn for MMP, which can result in delayed diagnoses or misdiagnoses. This review aims to integrate and present currently available data to clarify diagnostic strategies and to present diagnostic criteria for MMP. The ultimate blistering mechanism in MMP has not been elucidated, and such mechanism is especially obscure in COL17-type MMP. In bullous pemphigoid (BP), which is the most common autoimmune subepidermal blistering disease, some patients show oral lesion as well as predominant skin lesions. However, there is no fundamental explanation for the onset of oral lesions in BP. This article summarizes innovative research perspectives on the pathogenesis of oral lesions in pemphigoid. Finally, we propose a potential pathogenesis for COL17-type MMP.
Topics: Animals; Autoimmunity; Biomarkers; Blister; Humans; Mouth Mucosa; Mucous Membrane; Pemphigoid, Bullous; Severity of Illness Index
PubMed: 30740099
DOI: 10.3389/fimmu.2019.00034 -
Journal of Interferon & Cytokine... Feb 2017Several chemokines have important functions in mucosal immunity. While there are many chemokines, 4 of them (CCL25, CCL28, CXCL14, and CXCL17) are especially important... (Review)
Review
Several chemokines have important functions in mucosal immunity. While there are many chemokines, 4 of them (CCL25, CCL28, CXCL14, and CXCL17) are especially important in mucosal immunity because they are homeostatically expressed in mucosal tissues. Of these, only CCL25 and CCL28 have been widely recognized as mucosal chemokines. In this study, we review the physiology of these chemokines with specific emphasis on their function in mucosal immunity. CCL25 recruits certain important subsets of T cells that express CCR9 to the small intestine. These CCR9 T cells also express the integrin α4β7 and have been shown to play important roles in the control of intestinal inflammation. CCL28 recruits CCR10 IgA plasmablasts to the lactating mammary gland. The role of CXCL14 in mucosal immunity is less well defined, but a Cxcl14 mouse exhibits significant metabolic abnormalities. Finally, CXCL17 was the last chemokine to be described and signals through a new chemokine receptor (GPR35/CXCR8), which is expressed in a subset of macrophages that are recruited to mucosal tissues by this chemokine. We conclude that these 4 chemokines play very important roles in mucosal immunity and their continued functional characterization will likely identify novel therapeutic targets.
Topics: Adaptive Immunity; Animals; Biomarkers; Chemokines; Disease Susceptibility; Gene Expression Regulation; Humans; Immunity, Innate; Immunity, Mucosal; Mucous Membrane; Signal Transduction
PubMed: 28207301
DOI: 10.1089/jir.2016.0076 -
JAMA Dermatology Jan 2022Mucous membrane pemphigoid (MMP) is a rare, heterogeneous subepithelial autoimmune bullous disease. The association between its clinical and immunological features is...
IMPORTANCE
Mucous membrane pemphigoid (MMP) is a rare, heterogeneous subepithelial autoimmune bullous disease. The association between its clinical and immunological features is yet to be fully evaluated.
OBJECTIVES
To characterize the clinical, immunoserological, and immunopathological characteristics of patients with MMP and to identify site- and autoantigen-specific characteristics.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective cohort study encompassing all consecutive patients diagnosed with MMP from January 2007 through February 2020 in 2 tertiary referral centers in Germany.
MAIN OUTCOMES AND MEASURES
The clinical, immunoserological, and immunopathological features of eligible patients were evaluated. Associations of different anatomical sites and autoantigens were assessed using a multivariable logistic regression model.
RESULTS
The study encompassed 154 patients (96 [62.3%] women and 58 [37.7%] men; mean [SD] age at diagnosis, 66.2 [13.8] years) with MMP, of whom 125 (81.2%), 61 (39.6%), 34 (22.1%), and 16 (10.4%) presented with lesions involving the oral, ocular, nasal, and genital mucosae, respectively, and 35 (22.7%) presented with cutaneous involvement. Among the 154 patients, the most frequently targeted antigen was BP180 (90 patients [58.4%]), followed by laminin 332 (13 patients [8.4%]) and BP230 (3 patients [1.9%]). Ocular disease was inversely associated with oral (adjusted odds ratio [aOR], 0.02; 95% CI, 0.01-0.13) and nasal (aOR, 0.20; 95% CI, 0.04-0.91) involvement and was associated with a 13-fold increased risk of malignant neoplasm (aOR, 13.07; 95% CI, 1.56-109.36). Anti-laminin 332 reactivity was associated with malignant neoplasm (aOR, 23.27; 95% CI, 1.83-296.68), whereas anti-BP180 NC16A immunoglobulin G seropositivity was associated with absence of ocular lesions (aOR, 0.09; 95% CI, 0.01-0.99).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients with MMP, malignant neoplasms were associated with ocular disease and anti-laminin 332 reactivity, suggesting potential benefit of malignant neoplasm screening in these patients.
Topics: Autoantibodies; Autoantigens; Female; Humans; Male; Mucous Membrane; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous; Retrospective Studies
PubMed: 34817539
DOI: 10.1001/jamadermatol.2021.4773 -
Current Biology : CB Aug 2017Hoytema van Konijnenburg and Mucida discuss development and function of intraepithelial lymphocytes, which are found within the epithelial layer of mucosal and barrier...
Hoytema van Konijnenburg and Mucida discuss development and function of intraepithelial lymphocytes, which are found within the epithelial layer of mucosal and barrier tissues.
Topics: Animals; Epithelial Cells; Humans; Intraepithelial Lymphocytes; Mucous Membrane
PubMed: 28787597
DOI: 10.1016/j.cub.2017.05.073 -
Journal of Molecular Medicine (Berlin,... Sep 2017Of the total human body's surface, the majority is internal surface, belonging to the lungs (100 m) and intestinal tract (400 m). In comparison, the external surface... (Review)
Review
Of the total human body's surface, the majority is internal surface, belonging to the lungs (100 m) and intestinal tract (400 m). In comparison, the external surface area, belonging to the skin, comprises less than 1% (2 m). Continuous exposure of the mucosal surface to external factors (e.g., pathogens, food particles) requires tight regulation to maintain homeostasis. MicroRNAs (miRNAs) have gained noticeable attention as playing important roles in maintaining the steady-state of tissues by modulating immune functions and inflammatory responses. Accordingly, associations have been found between miRNA expression levels and human health conditions and diseases. These findings have important implications in inflammatory diseases involving pulmonary and intestinal mucosa, such as acute lung injury or inflammatory bowel disease. In this review, we highlight the known biology of miRNAs and discuss the role of miRNAs in modulating mucosal defense and homeostasis. Additionally, we discuss miRNAs serving as potential therapeutic targets to treat immunological conditions, particularly mucosal inflammation.
Topics: Animals; Gene Expression Regulation; Humans; Immunity, Mucosal; Inflammation; Inflammatory Bowel Diseases; MicroRNAs; Mucous Membrane; Pneumonia; RNA Interference
PubMed: 28726085
DOI: 10.1007/s00109-017-1568-7 -
Cell May 2016Multidirectional interactions between the nervous and immune systems have been documented in homeostasis and pathologies ranging from multiple sclerosis to autism, and... (Review)
Review
Multidirectional interactions between the nervous and immune systems have been documented in homeostasis and pathologies ranging from multiple sclerosis to autism, and from leukemia to acute and chronic inflammation. Recent studies have addressed this crosstalk using cell-specific targeting, novel sequencing, imaging, and analytical tools, shedding light on unappreciated mechanisms of neuro-immune regulation. This Review focuses on neuro-immune interactions at barrier surfaces-mostly the gut, but also including the skin and the airways, areas densely populated by neurons and immune cells that constantly sense and adapt to tissue-specific environmental challenges.
Topics: Animals; Hematopoiesis; Humans; Immune System; Intestinal Mucosa; Intestines; Lymphoid Tissue; Mucous Membrane; Nervous System; Neurons
PubMed: 27153494
DOI: 10.1016/j.cell.2016.04.041 -
Journal of Immunology (Baltimore, Md. :... Oct 2021Metabolic diseases are common worldwide and include diseases of overnutrition, such as obesity, or undernutrition, such as kwashiorkor. Both the immune system and the... (Review)
Review
Metabolic diseases are common worldwide and include diseases of overnutrition, such as obesity, or undernutrition, such as kwashiorkor. Both the immune system and the microbiota contribute to a variety of metabolic diseases; however, these two processes have largely been studied independently of one another in this context. The gastrointestinal system houses the greatest density of microbes but also houses one of the largest collections of immune molecules, especially Abs. The IgA isotype dominates the Ab landscape at mucosal sites, and a number of studies have demonstrated the importance of this Ab to the stability of the microbiota. In this article, we review the literature that demonstrates how homeostatic Ab responses control microbiota composition and function to influence metabolic disease. We propose that many metabolic diseases may arise from disruptions to homeostatic immune control of gut commensals and that further understanding this interaction can offer a novel opportunity for therapeutic interventions.
Topics: Animals; Dysbiosis; Host Microbial Interactions; Humans; Immunity, Mucosal; Immunoglobulin A; Immunomodulation; Metabolic Diseases; Microbiota; Mucous Membrane
PubMed: 34544814
DOI: 10.4049/jimmunol.2100419 -
Seminars in Immunology May 2015Inflammatory diseases in mucosal organs as diverse as the lung, liver and intestine inevitably require the intimate interactions between neutrophils and epithelia. The... (Review)
Review
Inflammatory diseases in mucosal organs as diverse as the lung, liver and intestine inevitably require the intimate interactions between neutrophils and epithelia. The physiologic consequences of such interactions often determine endpoint organ function, and for this reason, much recent interest has developed in identifying mechanisms and novel targets to promote the resolution of mucosal inflammation. Physiologically-relevant in vitro and in vivo model systems have aided in discovery of novel pathways to define basic inflammatory mechanisms and approaches to defining the concepts of inflammatory resolution. Here, we will review the recent literature regarding the contribution of neutrophils to inflammatory resolution, with an emphasis on the role of the tissue microenvironment, endogenous pathways for promoting resolution and the molecular determinants of neutrophil-epithelial cell interactions during ongoing inflammation. These recent studies highlight the dynamic nature of pro-resolving pathways and lend insight into the complexity of treating mucosal inflammation.
Topics: Cell Communication; Cell Hypoxia; Cell Movement; Cellular Microenvironment; Epithelial Cells; Homeostasis; Humans; Inflammation; Mucous Membrane; Neutrophils; Oxygen Consumption; Purine Nucleosides
PubMed: 25818531
DOI: 10.1016/j.smim.2015.03.007