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1.
BMJ Case Rep ; 17(6)2024 Jun 26.
Article de Anglais | MEDLINE | ID: mdl-38926124

RÉSUMÉ

A major complication with extracorporeal membrane oxygenation (ECMO) is bleeding which can occur in up to 40% of cases and can be life-threatening. Minor bleeding may be overlooked and under-reported. While some of the underlying mechanisms such as platelet injury and anticoagulation therapy have been identified, several other factors are still under-researched. Here, we describe a unique case of a subtle mucosal membrane bleeding that is found to be associated with vitamin C deficiency while on treatment with ECMO. Investigating vitamin C levels may be useful in understanding causes of bleeding in some patients on ECMO therapy, particularly if there are risk factors for malnutrition.


Sujet(s)
Carence en acide ascorbique , Oxygénation extracorporelle sur oxygénateur à membrane , Humains , Oxygénation extracorporelle sur oxygénateur à membrane/effets indésirables , Oxygénation extracorporelle sur oxygénateur à membrane/méthodes , Carence en acide ascorbique/complications , Mâle , Hémorragie/étiologie , Hémorragie/thérapie , Acide ascorbique/usage thérapeutique , Femelle , Adulte d'âge moyen , Muqueuse
2.
J Immunother Cancer ; 12(6)2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38908858

RÉSUMÉ

BACKGROUND: Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers. METHODS: We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR). RESULTS: Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response. CONCLUSION: Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023277.


Sujet(s)
Anticorps monoclonaux humanisés , Protocoles de polychimiothérapie antinéoplasique , Mélanome , Pyridines , Humains , Mâle , Femelle , Mélanome/traitement médicamenteux , Mélanome/anatomopathologie , Pyridines/usage thérapeutique , Pyridines/administration et posologie , Pyridines/pharmacologie , Pyridines/effets indésirables , Adulte d'âge moyen , Anticorps monoclonaux humanisés/usage thérapeutique , Anticorps monoclonaux humanisés/effets indésirables , Sujet âgé , Adulte , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Muqueuse/effets des médicaments et des substances chimiques , Muqueuse/anatomopathologie
3.
Dev Comp Immunol ; 158: 105210, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38844187

RÉSUMÉ

Interleukin (IL) 20 is a multifunctional cytokine and plays a vital role in regulating autoimmune diseases, inflammation, and immune responses. IL-20 homologs have been described in fish. However, due to the lack of antibodies, cellular sources and immunological functions of fish IL-20 in response to infections have not been fully characterized. In this study, a monoclonal antibody (mAb) was generated against the recombinant grass carp (Ctenopharyngodon idella) IL-20 protein and characterized by immunoblotting, immunofluorescent microscopy and flow cytometry. It was shown that the IL-20 mAb specifically recognized recombinant IL-20 proteins expressed in the E. coli cells and HEK293 cells. Using confocal microscopy, the IL-20+ cells were identified in the head kidney, gills and intestine of grass carp, and induced after infection with Aeromonas hydrophila. Moreover, the IL-20 protein was found to be secreted mainly by CD3γδ T cells which were located predominantly in the gill filaments and intestinal mucosa. Taken together, our results suggest that IL-20 producing T cells are required for the mucosal immunity against bacterial infection in fish.


Sujet(s)
Aeromonas hydrophila , Carpes (poisson) , Maladies des poissons , Protéines de poisson , Infections bactériennes à Gram négatif , Immunité muqueuse , Interleukines , Animaux , Carpes (poisson)/immunologie , Carpes (poisson)/microbiologie , Aeromonas hydrophila/immunologie , Infections bactériennes à Gram négatif/immunologie , Infections bactériennes à Gram négatif/médecine vétérinaire , Maladies des poissons/immunologie , Maladies des poissons/microbiologie , Protéines de poisson/immunologie , Protéines de poisson/métabolisme , Protéines de poisson/génétique , Humains , Interleukines/métabolisme , Interleukines/immunologie , Cellules HEK293 , Branchies/immunologie , Branchies/métabolisme , Antigènes CD3/immunologie , Antigènes CD3/métabolisme , Anticorps monoclonaux/immunologie , Muqueuse intestinale/immunologie , Muqueuse intestinale/microbiologie , Lymphocytes T/immunologie , Muqueuse/immunologie
4.
Methods Mol Biol ; 2807: 299-323, 2024.
Article de Anglais | MEDLINE | ID: mdl-38743237

RÉSUMÉ

Ex vivo cervical tissue explant models offer a physiologically relevant approach for studying virus-host interactions that underlie mucosal HIV-1 transmission to women. However, the utility of cervical explant tissue (CET) models has been limited for both practical and technical reasons. These include assay variation, inadequate sensitivity for assessing HIV-1 infection and replication in tissue, and constraints imposed by the requirement for using multiple replica samples of CET to test each experimental variable and assay parameter. Here, we describe an experimental approach that employs secreted nanoluciferase (sNLuc) and current HIV-1 reporter virus technologies to overcome certain limitations of earlier ex vivo CET models. This method augments application of the CET model for investigating important questions involving mucosal HIV-1 transmission.


Sujet(s)
Col de l'utérus , Infections à VIH , VIH-1 (Virus de l'Immunodéficience Humaine de type 1) , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/physiologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/génétique , Humains , Col de l'utérus/virologie , Col de l'utérus/métabolisme , Femelle , Infections à VIH/virologie , Luciferases/génétique , Luciferases/métabolisme , Gènes rapporteurs , Muqueuse/virologie , Muqueuse/métabolisme , Réplication virale
5.
Cancer Res Commun ; 4(5): 1351-1362, 2024 May 28.
Article de Anglais | MEDLINE | ID: mdl-38695555

RÉSUMÉ

Mucosal melanoma exhibits limited responsiveness to anti-PD-1 therapy. However, a subgroup of mucosal melanomas, particularly those situated at specific anatomic sites like primary malignant melanoma of the esophagus (PMME), display remarkable sensitivity to anti-PD-1 treatment. The underlying mechanisms driving this superior response and the DNA methylation patterns in mucosal melanoma have not been thoroughly investigated. We collected tumor samples from 50 patients with mucosal melanoma, including 31 PMME and 19 non-esophageal mucosal melanoma (NEMM). Targeted bisulfite sequencing was conducted to characterize the DNA methylation landscape of mucosal melanoma and explore the epigenetic profiling differences between PMME and NEMM. Bulk RNA sequencing and multiplex immunofluorescence staining were performed to confirm the impact of methylation on gene expression and immune microenvironment. Our analysis revealed distinct epigenetic signatures that distinguish mucosal melanomas of different origins. Notably, PMME exhibited distinct epigenetic profiling characterized by a global hypermethylation alteration compared with NEMM. The prognostic model based on the methylation scores of a 7-DMR panel could effectively predict the overall survival of patients with PMME and potentially serve as a prognostic factor. PMME displayed a substantial enrichment of immune-activating cells in contrast to NEMM. Furthermore, we observed hypermethylation of the TERT promoter in PMME, which correlated with heightened CD8+ T-cell infiltration, and patients with hypermethylated TERT were likely to have improved responses to immunotherapy. Our results indicated that PMME shows a distinct methylation landscape compared with NEMM, and the epigenetic status of TERT might be used to estimate prognosis and direct anti-PD-1 treatment for mucosal melanoma. SIGNIFICANCE: This study investigated the intricate epigenetic factor of mucosal melanomas contributed to the differential immune checkpoint inhibitor response, and found that PMME exhibited a global hypermethylation pattern and lower gene expression in comparison to NEMM. TERT hypermethylation may contribute to the favorable responses observed in patients with mucosal melanoma undergoing immunotherapy.


Sujet(s)
Méthylation de l'ADN , Épigenèse génétique , Mélanome , Humains , Mélanome/génétique , Mélanome/immunologie , Mélanome/anatomopathologie , Épigenèse génétique/génétique , Méthylation de l'ADN/génétique , Mâle , Femelle , Sujet âgé , Microenvironnement tumoral/immunologie , Microenvironnement tumoral/génétique , Muqueuse/immunologie , Muqueuse/anatomopathologie , Adulte d'âge moyen , Régulation de l'expression des gènes tumoraux , Pronostic , Lymphocytes TIL/immunologie , Tumeurs de l'oesophage/génétique , Tumeurs de l'oesophage/immunologie , Tumeurs de l'oesophage/anatomopathologie , Tumeurs de l'oesophage/mortalité , Telomerase/génétique
6.
Indian J Ophthalmol ; 72(6): 920, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38804806

RÉSUMÉ

BACKGROUND: A healthy lid-wiper is an important component of a healthy ocular surface. Any abnormality or irregularity of the lid wiper can potentially damage a relatively healthy ocular surface. Stevens-Johnson syndrome, toxic epidermal necrolysis, and ocular cicatricial pemphigoid are some of the examples that can result in lid-margin keratinization during the course of the disease. These permanent changes at the lid margin mechanically abrade the corneal surface and facilitate corneal neovascularization. The corneal clarity is lost over time, and the patients have corneal blindness. PURPOSE: This video discusses the role of a healthy lid-wiper, conditions causing lid-margin keratinization and subsequent lid-wiper keratopathy, and surgical technique in mucous membrane grafting. SYNOPSIS: The video demonstrates the technique of restoration of a healthy lid margin by doing a mucous membrane graft for lid-margin keratinization and its role in the prevention of corneal blindness. HIGHLIGHTS: Lid-margin keratinization is essentially a chronic sequela and is often ignored till irreversible corneal changes develop. Early intervention in the form of mucous membrane grafting can prevent corneal vascularization and loss of corneal clarity. VIDEO LINK: https://youtu.be/NGMlqUp_qLU.


Sujet(s)
Maladies de la cornée , Muqueuse , Humains , Maladies de la cornée/chirurgie , Maladies de la cornée/diagnostic , Muqueuse/chirurgie , Paupières/chirurgie , Maladies de la paupière/chirurgie , Procédures de chirurgie ophtalmologique/méthodes , Cornée/chirurgie
7.
Technol Cancer Res Treat ; 23: 15330338241257479, 2024.
Article de Anglais | MEDLINE | ID: mdl-38803309

RÉSUMÉ

Background & Objective: Assessment of muscularis propria invasion is a crucial step in the management of urothelial carcinoma since it necessitates aggressive treatment. The diagnosis of muscle invasion is a challenging process for pathologists. Artificial intelligence is developing rapidly and being implemented in various fields of pathology. The purpose of this study was to develop an algorithm for the detection of muscularis propria invasion in urothelial carcinoma. Methods: The Training cohort consisted of 925 images from 50 specimens of urothelial carcinoma. Ninety-seven images from 10 new specimens were used as a validation cohort. Clinical validation used 127 whole specimens with a total of 617 slides. The algorithm determined areas where tumor and muscularis propria events were in nearest proximity, and presented these areas to the pathologist. Results: Analytical evaluation showed a sensitivity of 72% for muscularis propria and 65% for tumor, and a specificity of 46% and 77% for muscularis propria and tumor detection, respectively. The incorporation of the spatial proximity factor between muscularis propria and tumor in the clinical validation significantly improved the detection of muscularis propria invasion, as the algorithm managed to identify all except for one case with muscle invasive bladder cancer in the clinical validation cohort. The case missed by the algorithm was nested urothelial carcinoma, a rare subtype with unusual morphologic features. The pathologist managed to identify muscle invasion based on the images provided by the algorithm in a short time, with an average of approximately 5 s. Conclusion: The algorithm we developed may greatly aid in accurate identification of muscularis propria invasion by imitating the thought process of the pathologist.


Sujet(s)
Algorithmes , Intelligence artificielle , Invasion tumorale , Tumeurs de la vessie urinaire , Humains , Tumeurs de la vessie urinaire/anatomopathologie , Tumeurs de la vessie urinaire/diagnostic , Carcinome transitionnel/anatomopathologie , Mâle , Femelle , Muqueuse/anatomopathologie , Sujet âgé , Adulte d'âge moyen
8.
Drug Metab Pharmacokinet ; 56: 100998, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38583388

RÉSUMÉ

To assess the pharmacologically relevant and selective muscarinic receptor occupancy in the bladder mucosa, we considered not only plasma drug concentrations but also urinary drug concentrations. The purpose of this study was to predict muscarinic receptor occupancy in the human bladder mucosa based on urinary concentrations in response to clinical dosages of antimuscarinic agents used to treat overactive bladder. The calculated mean plasma or serum unbound steady state concentrations were 0.06-11 nM in clinical dosages of five antimuscarinic agents. Urinary concentrations calculated from the mean plasma or serum and renal clearance ranged between 19 nM and 2 µM, which were >10-fold higher than the Ki values for bladder muscarinic receptors excluding propiverine. Bladder mucosal muscarinic receptor occupancy estimated from the urinary concentrations and the Ki values was >90 % at a steady state in clinical dosages of five antimuscarinic agents. The bladder muscarinic receptor occupancy was higher than that in the parotid gland calculated based on the mean plasma or serum unbound concentrations and Ki values for muscarinic receptors in the parotid gland. These results suggest that sufficient and selective muscarinic receptor occupancy by antimuscarinic agents, to exert pharmacological effects, in the bladder mucosa can be predicted using urinary concentrations.


Sujet(s)
Muqueuse , Antagonistes muscariniques , Récepteur muscarinique , Vessie hyperactive , Vessie urinaire , Humains , Antagonistes muscariniques/pharmacocinétique , Vessie hyperactive/traitement médicamenteux , Vessie hyperactive/métabolisme , Vessie hyperactive/urine , Récepteur muscarinique/métabolisme , Vessie urinaire/métabolisme , Vessie urinaire/effets des médicaments et des substances chimiques , Muqueuse/métabolisme , Muqueuse/effets des médicaments et des substances chimiques , Mâle , Femelle , Adulte d'âge moyen , Adulte , Sujet âgé
9.
Environ Res ; 252(Pt 3): 118930, 2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-38615788

RÉSUMÉ

Antibiotic resistance genes (ARGs) are a kind of emerging environmental contamination, and are commonly found in antibiotic application situations, attracting wide attention. Fish skin mucosal surface (SMS), as the contact interface between fish and water, is the first line of defense against external pollutant invasion. Antibiotics are widely used in aquaculture, and SMS may be exposed to antibiotics. However, what happens to SMS when antibiotics are applied, and whether ARGs are enriched in SMS are not clear. In this study, Zebrafish (Danio rerio) were exposed to antibiotic and antibiotic resistant bacteria in the laboratory to simulate the aquaculture situation, and the effects of SMS on the spread of ARGs were explored. The results showed that SMS maintained the stability of the bacterial abundance and diversity under apramycin (APR) and bacterial exposure effectively. Until 11 days after stopping APR exposure, the abundance of ARGs in SMS (mean value was 3.32 × 10-3 copies/16S rRNA copies) still did not recover to the initial stage before exposure, which means that enriched ARGs in SMS were persistently remained. Moreover, non-specific immunity played an important role in resisting infection of external contamination. Besides, among antioxidant proteins, superoxide dismutase showed the highest activity. Consequently, it showed that SMS became a barrier of antibiotic resistance genes under APR exposure, and ARGs in SMS were difficult to remove once colonized. This study provided a reference for understanding the transmission, enrichment process, and ecological impact of antibiotics and ARGs in aquatic environments.


Sujet(s)
Antibactériens , Nébramycine , Peau , Danio zébré , Animaux , Danio zébré/génétique , Nébramycine/analogues et dérivés , Nébramycine/pharmacologie , Antibactériens/pharmacologie , Antibactériens/toxicité , Peau/effets des médicaments et des substances chimiques , Peau/microbiologie , Résistance microbienne aux médicaments/génétique , Muqueuse/effets des médicaments et des substances chimiques , Muqueuse/microbiologie , Polluants chimiques de l'eau/toxicité
10.
Front Immunol ; 15: 1243566, 2024.
Article de Anglais | MEDLINE | ID: mdl-38686381

RÉSUMÉ

Background: Lichen planus pemphigoides (LPP), an association between lichen planus and bullous pemphigoid lesions, is a rare subepithelial autoimmune bullous disease. Mucous membrane involvement has been reported previously; however, it has never been specifically studied. Methods: We report on 12 cases of LPP with predominant or exclusive mucous membrane involvement. The diagnosis of LPP was based on the presence of lichenoid infiltrates in histology and immune deposits in the basement membrane zone in direct immunofluorescence and/or immunoelectron microscopy. Our systematic review of the literature, performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, highlights the clinical and immunological characteristics of LPP, with or without mucous membrane involvement. Results: Corticosteroids are the most frequently used treatment, with better outcomes in LPP with skin involvement alone than in that with mucous membrane involvement. Our results suggest that immunomodulators represent an alternative first-line treatment for patients with predominant mucous membrane involvement.


Sujet(s)
Lichen plan , Muqueuse , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Hormones corticosurrénaliennes/usage thérapeutique , Lichen plan/traitement médicamenteux , Lichen plan/anatomopathologie , Lichen plan/immunologie , Lichen plan/diagnostic , Muqueuse/anatomopathologie , Muqueuse/immunologie , Pemphigoïde bulleuse/immunologie , Pemphigoïde bulleuse/traitement médicamenteux , Pemphigoïde bulleuse/anatomopathologie , Pemphigoïde bulleuse/diagnostic
11.
Front Cell Infect Microbiol ; 14: 1231697, 2024.
Article de Anglais | MEDLINE | ID: mdl-38601739

RÉSUMÉ

The anti-COVID-19 intramuscular vaccination induces a strong systemic but a weak mucosal immune response in adults. Little is known about the mucosal immune response in children infected or vaccinated against SARS-CoV-2. We found that 28% of children had detectable salivary IgA against SARS-CoV-2 even before vaccination, suggesting that, in children, SARS-CoV-2 infection may be undiagnosed. After vaccination, only receptor-binding domain (RBD)-specific IgA1 significantly increased in the saliva. Conversely, infected children had significantly higher salivary RBD-IgA2 compared to IgA1, indicating that infection more than vaccination induces a specific mucosal immune response in children. Future efforts should focus on development of vaccine technologies that also activate mucosal immunity.


Sujet(s)
COVID-19 , Immunité muqueuse , Adulte , Enfant , Humains , SARS-CoV-2 , Immunoglobuline A , Muqueuse , Vaccination , Anticorps antiviraux
12.
Cells ; 13(7)2024 Apr 05.
Article de Anglais | MEDLINE | ID: mdl-38607072

RÉSUMÉ

The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the "classical" borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer-the process of tumor neoangiogenesis.


Sujet(s)
Carcinomes , Tumeurs du larynx , Humains , Tumeurs du larynx/génétique , Néovascularisation pathologique/génétique , Muqueuse , Facteurs de transcription à motif basique hélice-boucle-hélice/métabolisme
13.
In Vivo ; 38(3): 1112-1118, 2024.
Article de Anglais | MEDLINE | ID: mdl-38688609

RÉSUMÉ

BACKGROUND/AIM: Epitope H contains an O-linked N-acetylglucosamine (O-GlcNAcH) residue in a specific conformation or environment, recognized by a site-specific monoclonal mouse IgM antibody H. O-GlcNAcH occurs in several normal and pathological cells and in several polypeptides, including keratin-8 and vimentin, on the latter in cells under stress. MATERIALS AND METHODS: In this work, we studied the distribution of O-GlcNAcH on cells of endocervical mucosa in 60 specimens of endocervical curettings, 10 of which contained 15 inflamed polyps. RESULTS: In our results, expression of O-GlcNAcH was weak in the mucosa with <5% mucin-secreting cells and up to 30% of the polyps staining positively. All non-ciliated, non-mucin-secreting cells, normal and hyperplastic 'reserve' cells, as well as the cells of immature squamous metaplasia, showed strong diffuse cytoplasmic staining for O-GlcNAcH. In mature squamous epithelium, fewer than 5% of basal cells and all the intermediate and superficial cells showed cytoplasmic staining for O-GlcNAcH, whereas parabasal cells were negative. All ciliated cells showed patchy or diffuse cytoplasmic staining. Nuclear staining for O-GlcNAcH was weak with fewer than 5% of hyperplastic 'reserve' and ciliated cells staining positively. Moreover, mucosal fibroblasts were negative, whereas all stromal cells of the polyps showed strong cytoplasmic staining for O-GlcNAcH. CONCLUSION: O-GlcNAcH is: a) differentially expressed among the cellular elements of mucosa and polyps, b) upregulated in mucin-secreting cells of polyps, c) induced in stromal cells of inflamed polyps, and d) can be used as a marker to differentiate between 'reserve' (positive) and parabasal (negative) cells, which have similar morphology using conventional cytological stains.


Sujet(s)
Acétyl-glucosamine , Col de l'utérus , Épitopes , Muqueuse , Humains , Femelle , Acétyl-glucosamine/métabolisme , Col de l'utérus/anatomopathologie , Col de l'utérus/métabolisme , Épitopes/immunologie , Muqueuse/métabolisme , Muqueuse/anatomopathologie , Adulte , Adulte d'âge moyen , Immunohistochimie
14.
Nature ; 628(8009): 854-862, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38570678

RÉSUMÉ

The intestinal immune system is highly adapted to maintaining tolerance to the commensal microbiota and self-antigens while defending against invading pathogens1,2. Recognizing how the diverse network of local cells establish homeostasis and maintains it in the complex immune environment of the gut is critical to understanding how tolerance can be re-established following dysfunction, such as in inflammatory disorders. Although cell and molecular interactions that control T regulatory (Treg) cell development and function have been identified3,4, less is known about the cellular neighbourhoods and spatial compartmentalization that shapes microorganism-reactive Treg cell function. Here we used in vivo live imaging, photo-activation-guided single-cell RNA sequencing5-7 and spatial transcriptomics to follow the natural history of T cells that are reactive towards Helicobacter hepaticus through space and time in the settings of tolerance and inflammation. Although antigen stimulation can occur anywhere in the tissue, the lamina propria-but not embedded lymphoid aggregates-is the key microniche that supports effector Treg (eTreg) cell function. eTreg cells are stable once their niche is established; however, unleashing inflammation breaks down compartmentalization, leading to dominance of CD103+SIRPα+ dendritic cells in the lamina propria. We identify and validate the putative tolerogenic interaction between CD206+ macrophages and eTreg cells in the lamina propria and identify receptor-ligand pairs that are likely to govern the interaction. Our results reveal a spatial mechanism of tolerance in the lamina propria and demonstrate how knowledge of local interactions may contribute to the next generation of tolerance-inducing therapies.


Sujet(s)
Muqueuse intestinale , Muqueuse , Lymphocytes T régulateurs , Animaux , Femelle , Mâle , Souris , Antigènes CD/métabolisme , Cellules dendritiques/immunologie , Cellules dendritiques/métabolisme , Analyse de profil d'expression de gènes , Helicobacter hepaticus/immunologie , Infections à Helicobacter/immunologie , Infections à Helicobacter/microbiologie , Tolérance immunitaire/immunologie , Inflammation/immunologie , Inflammation/microbiologie , Inflammation/anatomopathologie , Intégrines alpha/métabolisme , Muqueuse intestinale/cytologie , Muqueuse intestinale/immunologie , Macrophages/immunologie , Macrophages/métabolisme , Souris de lignée C57BL , Muqueuse/cytologie , Muqueuse/immunologie , Récepteurs immunologiques/métabolisme , Récepteurs immunologiques/immunologie , Analyse de l'expression du gène de la cellule unique , Lymphocytes T régulateurs/immunologie , Lymphocytes T régulateurs/cytologie , Transcriptome
15.
Fish Shellfish Immunol ; 149: 109549, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38599365

RÉSUMÉ

The study was designed to investigate the effects of replacing fish oil by algal oil and rapeseed oil on histomorphology indices of the intestine, skin and gill, mucosal barrier status and immune-related genes of mucin and antimicrobial peptide (AMP) genes in Atlantic salmon (Salmo salar). For these purposes, Atlantic salmon smolts were fed three different diets. The first was a control diet containing fish oil but no Schizochytrium oil. In the second diet, almost 50 % of the fish oil was replaced with algal oil, and in the third diet, fish oil was replaced entirely with algal oil. The algal oil contained mostly docosahexaenoic acid (DHA) and some eicosapentaenoic acid (EPA). The study lasted for 49 days in freshwater (FW), after which some fish from each diet group were transferred to seawater (SW) for a 48-h challenge test at 33 ppt to test their ability to tolerate high salinity. Samples of skin, gills, and mid intestine [both distal (DI) and anterior (AI) portions of the mid intestine] were collected after the feeding trial in FW and after the SW-challenge test to assess the effects of the diets on the structure and immune functions of the mucosal surfaces. The results showed that the 50 % VMO (Veramaris® algal oil) dietary group had improved intestinal, skin, and gill structures. Principal component analysis (PCA) of the histomorphological parameters demonstrated a significant effect of the algal oil on the intestine, skin, and gills. In particular, the mucosal barrier function of the intestine, skin, and gills was enhanced in the VMO 50 % dietary group after the SW challenge, as evidenced by increased mucous cell density. Immunolabelling of heat shock protein 70 (HSP70) in the intestine (both DI and AI) revealed downregulation of the protein expression in the 50 % VMO group and a corresponding upregulation in the 100 % VMO group compared to 0 % VMO. The reactivity of HSP70 in the epithelial cells was higher after the SW challenge compared to the FW phase. Immune-related genes related to mucosal defense, such as mucin genes [muc2, muc5ac1 (DI), muc5ac1 (AI), muc5ac2, muc5b (skin), and muc5ac1 (gills)], and antimicrobial peptide genes [def3 (DI), def3 (AI), and cath1 (skin)] were significantly upregulated in the 50 % VMO group. PCA of gene expression demonstrated the positive influences on gene regulation in the 50 % VMO dietary group. In conclusion, this study demonstrated the positive effect of substituting 50 % of fish oil with algal oil in the diets of Atlantic salmon. The findings of histomorphometry, mucosal mapping, immunohistochemistry, and immune-related genes connected to mucosal responses all support this conclusion.


Sujet(s)
Aliment pour animaux , Régime alimentaire , Huile de colza , Salmo salar , Animaux , Salmo salar/immunologie , Régime alimentaire/médecine vétérinaire , Huile de colza/composition chimique , Aliment pour animaux/analyse , Muqueuse/immunologie , Huiles de poisson/administration et posologie , Peau/immunologie , Peau/effets des médicaments et des substances chimiques , Saisons , Branchies/immunologie , Branchies/effets des médicaments et des substances chimiques , Intestins/effets des médicaments et des substances chimiques , Intestins/immunologie
16.
Front Immunol ; 15: 1353556, 2024.
Article de Anglais | MEDLINE | ID: mdl-38571943

RÉSUMÉ

Natural killer (NK) cells, with a unique NK cell receptor phenotype, are abundantly present in the non-pregnant (endometrium) and pregnant (decidua) humanuterine mucosa. It is hypothesized that NK cells in the endometrium are precursors for decidual NK cells present during pregnancy. Microenvironmental changes can alter the phenotype of NK cells, but it is unclear whether decidual NK cell precursors in the endometrium alter their NK cell receptor repertoire under the influence of pregnancy. To examine whether decidual NK cell precursors reveal phenotypic modifications upon pregnancy, we immunophenotyped the NK cell receptor repertoire of both endometrial and early-pregnancy decidual NK cells using flow cytometry. We showed that NK cells in pre-pregnancy endometrium have a different phenotypic composition compared to NK cells in early-pregnancy decidua. The frequency of killer-immunoglobulin-like receptor (KIR expressing NK cells, especially KIR2DS1, KIR2DL2L3S2, and KIR2DL2S2 was significantly lower in decidua, while the frequency of NK cells expressing activating receptors NKG2D, NKp30, NKp46, and CD244 was significantly higher compared to endometrium. Furthermore, co-expression patterns showed a lower frequency of NK cells co-expressing KIR3DL1S1 and KIR2DL2L3S2 in decidua. Our results provide new insights into the adaptations in NK cell receptor repertoire composition that NK cells in the uterine mucosa undergo upon pregnancy.


Sujet(s)
Endomètre , Cellules tueuses naturelles , Grossesse , Femelle , Humains , Récepteurs de cellules tueuses naturelles , Utérus , Muqueuse
17.
Nat Microbiol ; 9(5): 1231-1243, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38649413

RÉSUMÉ

The 2022 mpox virus (MPXV) outbreak was sustained by human-to-human transmission; however, it is currently unclear which factors lead to sustained transmission of MPXV. Here we present Mastomys natalensis as a model for MPXV transmission after intraperitoneal, rectal, vaginal, aerosol and transdermal inoculation with an early 2022 human outbreak isolate (Clade IIb). Virus shedding and tissue replication were route dependent and occurred in the presence of self-resolving localized skin, lung, reproductive tract or rectal lesions. Mucosal inoculation via the rectal, vaginal and aerosol routes led to increased shedding, replication and a pro-inflammatory T cell profile compared with skin inoculation. Contact transmission was higher from rectally inoculated animals. This suggests that transmission might be sustained by increased susceptibility of the anal and genital mucosae for infection and subsequent virus release.


Sujet(s)
Muqueuse , Infections à Poxviridae , Excrétion virale , Animaux , Femelle , Muqueuse/virologie , Infections à Poxviridae/transmission , Infections à Poxviridae/virologie , Infections à Poxviridae/médecine vétérinaire , Humains , Réplication virale , Modèles animaux de maladie humaine , Rodentia/virologie , Mâle , Rats , Vagin/virologie , Épidémies de maladies
18.
Surg Endosc ; 38(5): 2497-2504, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38466423

RÉSUMÉ

INTRODUCTION: Since patients with pharyngeal squamous cell carcinoma (SCC) often have multiple pharyngeal lesions, evaluation of pharyngeal lesions before endoscopic resection (ER) is important. However, detailed endoscopic observation of the entire pharyngeal mucosa under conscious sedation is difficult. We examined the usefulness of endoscopic surveillance with narrow band imaging (NBI) and lugol staining for detection of pharyngeal sublesions during ER for pharyngeal SCC under general anesthesia (endoscopic surveillance during treatment; ESDT). METHODS: From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT. RESULTS: Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the ESDT and 10 (12.8%) (95% CI 6.9-22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining. CONCLUSIONS: Endoscopic surveillance for pharyngeal sublesions during ER for pharyngeal SCC is feasible and useful.


Sujet(s)
Tumeurs du pharynx , Humains , Mâle , Femelle , Tumeurs du pharynx/chirurgie , Tumeurs du pharynx/anatomopathologie , Tumeurs du pharynx/imagerie diagnostique , Études prospectives , Sujet âgé , Adulte d'âge moyen , Imagerie à bande étroite/méthodes , Carcinome épidermoïde/chirurgie , Carcinome épidermoïde/anatomopathologie , Carcinome épidermoïde/imagerie diagnostique , Muqueuse/anatomopathologie , Muqueuse/chirurgie , Iodures , Sujet âgé de 80 ans ou plus , Mucosectomie endoscopique/méthodes , Pharynx/anatomopathologie , Pharynx/imagerie diagnostique
19.
Mucosal Immunol ; 17(3): 402-415, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38521413

RÉSUMÉ

The microbiome has emerged as a crucial modulator of host-immune interactions and clearly impacts tumor development and therapy efficacy. The microbiome is a double-edged sword in cancer development and therapy as both pro-tumorigenic and anti-tumorigenic bacterial taxa have been identified. The staggering number of association-based studies in various tumor types has led to an enormous amount of data that makes it difficult to identify bacteria that promote tumor development or modulate therapy efficacy from bystander bacteria. Here we aim to comprehensively summarize the current knowledge of microbiome-host immunity interactions and cancer therapy in various mucosal tissues to find commonalities and thus identify potential functionally relevant bacterial taxa. Moreover, we also review recent studies identifying specific bacteria and mechanisms through which the microbiome modulates cancer development and therapy efficacy.


Sujet(s)
Immunothérapie , Microbiote , Tumeurs , Humains , Immunothérapie/méthodes , Animaux , Tumeurs/immunologie , Tumeurs/thérapie , Tumeurs/microbiologie , Tumeurs/étiologie , Microbiote/immunologie , Muqueuse/immunologie , Muqueuse/microbiologie , Interactions hôte-pathogène/immunologie , Microbiome gastro-intestinal/immunologie , Immunité muqueuse
20.
BMJ Case Rep ; 17(3)2024 Mar 25.
Article de Anglais | MEDLINE | ID: mdl-38531555

RÉSUMÉ

Lobular capillary haemangioma (LCH), previously known as pyogenic granuloma, is a benign vascular tumour of the skin or mucosa. We report a patient with spontaneous eruption of LCH, a rare occurrence, which resolved probably due to reverse koebnerisation.


Sujet(s)
Granulome pyogénique , Tumeurs vasculaires , Humains , Granulome pyogénique/anatomopathologie , Peau/anatomopathologie , Muqueuse/anatomopathologie
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