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Mucosal Immunology May 2018Interleukin (IL)-17A is a pro-inflammatory cytokine in mice and humans. It is recognized as a key factor for the protection of mice against various pathogens, but it... (Review)
Review
Interleukin (IL)-17A is a pro-inflammatory cytokine in mice and humans. It is recognized as a key factor for the protection of mice against various pathogens, but it also underlies pathogenic inflammatory responses in numerous mouse models. The inborn errors of IL-17A- and IL-17F-mediated immunity identified in humans in the last decade have revealed that IL-17A and IL-17F are key players in mucocutaneous immunity to Candida albicans, and, to a lesser extent, Staphylococcus aureus. By contrast, there is currently no genetic evidence for a causal link between excess of IL-17 and autoimmunity, autoinflammation, or allergy in humans. We discuss here the physiological and pathological roles of mouse and human IL-17A and IL-17F in host defense and excessive inflammation. We highlight recent advances in our understanding of the consequences of deficient or excessive IL-17 immunity at various mucocutaneous sites, including the oral cavity, skin, intestine, lungs, and vagina.
Topics: Animals; Communicable Diseases; Disease Models, Animal; Host-Pathogen Interactions; Humans; Immunity, Mucosal; Inflammation; Interleukin-17; Mice; Mucous Membrane
PubMed: 29186107
DOI: 10.1038/mi.2017.97 -
Clinical & Developmental Immunology 2011Interactions between mucosal surfaces and microbial microbiota are key to host defense, health, and disease. These surfaces are exposed to high numbers of microbes and... (Review)
Review
Interactions between mucosal surfaces and microbial microbiota are key to host defense, health, and disease. These surfaces are exposed to high numbers of microbes and must be capable of distinguishing between those that are beneficial or avirulent and those that will invade and cause disease. Our understanding of the mechanisms involved in these discriminatory processes has recently begun to expand as new studies bring to light the importance of epithelial cells and novel immune cell subsets such as T(h)17 T cells in these processes. Elucidating how these mechanisms function will improve our understanding of many diverse diseases and improve our ability to treat patients suffering from these conditions. In our voyage to discover these mechanisms, mucosal interactions with opportunistic commensal organisms such as the fungus Candida albicans provide insights that are invaluable. Here, we review current knowledge of the interactions between C. albicans and epithelial surfaces and how this may shape our understanding of microbial-mucosal interactions.
Topics: Animals; Candida albicans; Candidiasis; Cytokines; Epithelial Cells; Humans; Immunity, Mucosal; Mucous Membrane; Signal Transduction
PubMed: 21776285
DOI: 10.1155/2011/346307 -
Frontiers in Immunology 2019Bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP) are rare chronic autoimmune disorders characterized by subepidermal blistering. For the United States, there...
Bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP) are rare chronic autoimmune disorders characterized by subepidermal blistering. For the United States, there is a limited amount of studies in BP and MMP that address disease demographics and clinical data. In order to more comprehensively examine disease demographics and clinical factors, we performed a retrospective analysis of patient-reported data of 138 BP and 165 MMP patients enrolled in the International Pemphigus & Pemphigoid Foundation (IPPF) disease registry from 2010-2016. Patient-reported data was compared to Physician/Investigator reported data generated in our own local patient population (Western New York; 19 BP and 43 MMP patients). We confirm a female predominance in BP (M:F ratio 1:2.1) and MMP (M:F ratio 1:4.3), and a late onset within the 6th decade of life (average age at diagnosis, 59.1 ± 17.5 years for BP and 54.8 ± 11.2 years for MMP). MMP patients were significantly more likely to have a delay in diagnosis >12 months than BP patients (38 vs. 21%, respectively). Similar to other autoimmune conditions, a large number of BP (34%) and MMP (35%) patients present with other co-existing autoimmune disorders, with the most common being thyroid disease for both groups. Increased illness activity was paralleled by an increase in severe limitations of daily activities. The vast majority of of both BP and MMP patients received high intensity immunosuppression (49%). However, the majority of BP patients reported therapy with prednisone combined with other immunosuppressants (40%), while the majority of MMP patients received immunosuppressants other than prednisone (55%). With the exception of age at diagnosis, the clinical and demographic findings from both the national and local datasets were largely consistent with each other, and support those reported in other countries.
Topics: Aged; Autoantibodies; Autoimmune Diseases; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mucous Membrane; Patient Reported Outcome Measures; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous; Prednisone; Registries; Retrospective Studies
PubMed: 31608053
DOI: 10.3389/fimmu.2019.02219 -
Basic & Clinical Pharmacology &... Oct 2016The internal face of the detrusor smooth muscle wall of the urinary bladder is covered by a mucosa, separating muscle from the hostile environment of urine. However, the... (Review)
Review
The internal face of the detrusor smooth muscle wall of the urinary bladder is covered by a mucosa, separating muscle from the hostile environment of urine. However, the mucosa is more than a very low permeability structure and offers a sensory function that monitors the extent of bladder filling and composition of the urine. The mucosa may be considered as a single functional structure and comprises a tight epithelial layer under which is a basement membrane and lamina propria. The latter region itself is a complex of afferent nerves, blood vessels, interstitial cells and in some species including human beings a muscularis mucosae. Stress on the bladder wall through physical or chemical stressors elicits release of chemicals, such as ATP, acetylcholine, prostaglandins and nitric oxide that modulate the activity of either afferent nerves or the muscular components of the bladder wall. The release and responses are graded so that the mucosa forms a dynamic sensory structure, and there is evidence that the gain of this system is increased in pathologies such as overactive bladder and bladder pain syndrome. This system therefore potentially provides a number of drug targets against these conditions, once a number of fundamental questions are answered. These include how is mediator release regulated; what are the intermediate roles of interstitial cells that surround afferent nerves and blood vessels; and what is the mode of communication between urothelium and muscle - by diffusion of mediators or by cell-to-cell communication?
Topics: Animals; Humans; Models, Biological; Mucous Membrane; Muscle Contraction; Muscle, Smooth; Neurons, Afferent; Urinary Bladder; Urinary Bladder Diseases; Urinary Bladder, Overactive; Urothelium
PubMed: 27228303
DOI: 10.1111/bcpt.12626 -
Frontiers in Immunology 2019Paraneoplastic pemphigus (PNP) is a rare but life-threatening mucocutaneous disease mediated by paraneoplastic autoimmunity. Various neoplasms are associated with PNP.... (Review)
Review
Paraneoplastic pemphigus (PNP) is a rare but life-threatening mucocutaneous disease mediated by paraneoplastic autoimmunity. Various neoplasms are associated with PNP. Intractable stomatitis and polymorphous cutaneous eruptions, including blisters and lichenoid dermatitis, are characteristic clinical features caused by humoral and cell-mediated autoimmune reactions. Autoreactive T cells and IgG autoantibodies against heterogeneous antigens, including plakin family proteins and desmosomal cadherins, contribute to the pathogenesis of PNP. Several mechanisms of autoimmunity may be at play in this disease on the type of neoplasm present. Diagnosis can be made based on clinical and histopathological features, the presence of anti-plakin autoantibodies, and underlying neoplasms. Immunosuppressive agents and biologics including rituximab have been used for the treatment of PNP; however, the prognosis is poor due to underlying malignancies, severe infections during immunosuppressive treatment, and bronchiolitis obliterans mediated by autoimmunity. In this review, we overview the characteristics of PNP and focus on the immunopathology and the potential pathomechanisms of this disease.
Topics: Animals; Autoantibodies; Autoantigens; Autoimmunity; Biopsy; Disease Management; Disease Susceptibility; Humans; Mucous Membrane; Paraneoplastic Syndromes; Pemphigus; Prognosis; Skin; Symptom Assessment
PubMed: 31214197
DOI: 10.3389/fimmu.2019.01259 -
Frontiers in Immunology 2018
Topics: Animals; Cell Communication; Epithelial Cells; Humans; Immunity, Mucosal; Inflammatory Bowel Diseases; Intestinal Mucosa; Mucous Membrane; T-Lymphocytes; Wound Healing
PubMed: 29899742
DOI: 10.3389/fimmu.2018.01171 -
Mucosal Immunology Sep 2021During the last 20 years, a new field of research delineating the importance of the microbiota in health and diseases has emerged. Inappropriate host-microbiota... (Review)
Review
During the last 20 years, a new field of research delineating the importance of the microbiota in health and diseases has emerged. Inappropriate host-microbiota interactions have been shown to trigger a wide range of chronic inflammatory diseases, and defining the exact mechanisms behind perturbations of such relationship, as well as ways by which these disturbances can lead to disease states, both remain to be fully elucidated. The mucosa-associated microbiota constitutes a recently studied microbial population closely linked with the promotion of chronic intestinal inflammation and associated disease states. This review will highlight seminal works that have brought into light the importance of the mucosa-associated microbiota in health and diseases, emphasizing the challenges and promises of expending the mucosal microbiology field of research.
Topics: Age Factors; Animals; Biomarkers; Disease Susceptibility; Energy Metabolism; Gastrointestinal Microbiome; Homeostasis; Host Microbial Interactions; Host-Pathogen Interactions; Humans; Microbial Interactions; Microbiota; Mucous Membrane; Organ Specificity
PubMed: 33772148
DOI: 10.1038/s41385-021-00383-w -
Journal of Immunology Research 2015The epithelium regulates the interaction between the noxious xenogenous, as well as the microbial environment and the immune system, not only by providing a barrier but... (Review)
Review
The epithelium regulates the interaction between the noxious xenogenous, as well as the microbial environment and the immune system, not only by providing a barrier but also by expressing a number of immunoregulatory membrane receptors, and intracellular danger sensors and their downstream effectors. Amongst these are a number of inflammasome sensor subtypes, which have been initially characterized in myeloid cells and described to be activated upon assembly into multiprotein complexes by microbial and environmental triggers. This review compiles a vast amount of literature that supports a pivotal role for inflammasomes in the various epithelial barriers of the human body as essential factors maintaining immune signaling and homeostasis.
Topics: Animals; Epithelial Cells; Epithelium; Homeostasis; Host-Pathogen Interactions; Humans; Inflammasomes; Mucous Membrane; Signal Transduction; Skin
PubMed: 26355424
DOI: 10.1155/2015/828264 -
Allergology International : Official... Oct 2019Eosinophilic gastrointestinal diseases (EGIDs) are divided into eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), depending on the involved... (Review)
Review
Eosinophilic gastrointestinal diseases (EGIDs) are divided into eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), depending on the involved gastrointestinal tract, though both are considered to be chronic Th2-type allergic diseases caused by food or environmental allergens. In development of EoE, refluxed gastric acid may also have an important role. For diagnosis of EGIDs, the presence of symptoms possibly originating from the involved gastrointestinal tract and dense eosinophil infiltration are important factors. Imaging studies, including endoscopy and computed tomography, along with histopathological examinations of biopsy specimens are useful for diagnosis, whereas laboratory testing of blood, urine, and stool samples has limited value. Three useful options for treating EoE patients are acid inhibitors, swallowed topical corticosteroids, and an elimination diet, while systemic administration of glucocorticoids is the standard treatment of EGE, though information is limited. Since the prevalence of EGIDs is increasing in Western countries as well as Japan, development of effective treatments based on sufficient evidence is becoming an urgent need.
Topics: Animals; Combined Modality Therapy; Disease Management; Disease Susceptibility; Endoscopy, Gastrointestinal; Eosinophilia; Eosinophils; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Mucous Membrane
PubMed: 31000445
DOI: 10.1016/j.alit.2019.03.003 -
Biomedicine & Pharmacotherapy =... Jun 2020dl-Mandelic acid (MA), an alpha-hydroxycarboxylic acid, has been widely used as an intermediate of pharmaceutical and fine chemicals. Here, we evaluated the... (Review)
Review
dl-Mandelic acid (MA), an alpha-hydroxycarboxylic acid, has been widely used as an intermediate of pharmaceutical and fine chemicals. Here, we evaluated the sperm-immobilizing activity of MA and its safety profiles. Spermatozoon motility was assessed by computer-aided sperm analysis, the integrity of the plasma membrane and. mitochondrial potential was assessed using fluorescein isothiocyanate-pisum sativum agglutinin and JC-1, respectively. The local tolerance of the MA-containing gel formulation was evaluated using a rabbit vaginal irritation test. We found that MA inhibited sperm motility and movement patterns in a concentration-dependent manner. Within 20 s, MA-induced spermatozoa immobilization occurred with a minimum effective concentration and a median effective concentration of 0.86 and 0.54 mg/mL, respectively. Plasma membrane disruptions of MA-treated spermatozoa were relatively mild, but mitochondrial depolarization occurred. Histopathological examination showed that MA exposure did not exert obvious effects on the integrity of spermatozoa membrane structures and only caused slight irritation to the rabbit vaginal epithelium. The vaginal irritation scores of the vehicle control and the nonoxynol -9 gel control groups were 1.38 ± 0.65 and 7.88 ± 1.67, respectively (p < 0.01), whereas those of the MA gel groups at 10, 20, and 40 mg/mL were 1.69 ± 1.04, 2.98 ± 0.77, and 4.35 ± 1.04 with p values of >0.05, >0.05, and <0.05 (vs. vehicle control), respectively, which were within the clinically acceptable range (<8). Therefore, our results confirmed that MA exhibited significant sperm-immobilizing effects and caused mild plasma membrane injury, suggesting that it has potential for development as a future non-surfactant spermicide.
Topics: Animals; Cell Proliferation; Contraception; Dose-Response Relationship, Drug; Female; Humans; Male; Mandelic Acids; Membrane Potential, Mitochondrial; Mucous Membrane; Rabbits; Sperm Motility; Spermatocidal Agents; Spermatozoa; Vagina
PubMed: 32224371
DOI: 10.1016/j.biopha.2020.110104