Mechanisms of innate immune activation by gluten peptide p31-43 in mice

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Innate immunity contributes to the pathogenesis of CD, but the mechanisms remain poorly understood. Although previous in vitro work suggests that gliadin peptide p31-43 acts as an innate immune trigger, the underlying pathways are unclear and have not been explored in vivo. Here we show that intraluminal delivery of p31-43 induces morphological changes in the small intestinal mucosa of normal mice consistent with those seen in CD, including increased cell death and expression of inflammatory mediators. The effects of p31-43 were dependent on MyD88 and type I IFNs, but not Toll-like receptor 4 (TLR4), and were enhanced by coadministration of the TLR3 agonist polyinosinic:polycytidylic acid. Together, these results indicate that gliadin peptide p31-43 activates the innate immune pathways in vivo, such as IFN-dependent inflammation, relevant to CD. Our findings also suggest a common mechanism for the potential interaction between dietary gluten and viral infections in the pathogenesis of CD

Statement of the Prolamin Working Group on the Determination of Gluten in Fermented Foods Containing Partially Hydrolyzed Gluten

On August 12, 2020, the U.S. Food and Drug Administration (FDA) has finalized a rule related to gluten-free labeling for foods containing fermented, hydrolyzed ingredients. The FDA believes that there is no scientifically valid analytical method effective for determining gluten in fermented or hydrolyzed foods. In the absence of an analytical method, the FDA has decided to evaluate gluten-free claims on these foods based only on evidence that the food or ingredient used is gluten-free before fermentation or hydrolysis. For example, barley-based beers from which gluten is removed during brewing using special filtration, adsorption and/or enzymatic treatment are therefore excluded from bearing a gluten-free label

Broad MICA/B expression in the small bowel mucosa: a link between cellular stress and celiac disease

The MICA/B genes (MHC class I chain related genes A and B) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B+ T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B+ B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in in vitro models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role.Fil: Allegretti, Yessica Lorena. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bondar, Constanza María. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guzmán, Luciana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Cueto Rua, Eduardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Chopita, Nestor. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martin; ArgentinaFil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Zwirner, Norberto Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; ArgentinaFil: Chirdo, Fernando Gabriel. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers.DFG, 389687267, Kompartimentalisierung, Aufrechterhaltung und Reaktivierung humaner Gedächtnis-T-Lymphozyten aus Knochenmark und peripherem BlutDFG, 80750187, SFB 841: Leberentzündungen: Infektion, Immunregulation und KonsequenzenEC/H2020/800924/EU/International Cancer Research Fellowships - 2/iCARE-2DFG, 252623821, Die Rolle von follikulären T-Helferzellen in T-Helferzell-Differenzierung, Funktion und PlastizitätDFG, 390873048, EXC 2151: ImmunoSensation2 - the immune sensory syste

Enfermedad celíaca. Nuevas perspectivas terapéuticas basadas en un mejor conocimiento de su patogenia molecular

La enfermedad celíaca (EC) es una patología gastrointestinal crónica de tipo autoinmune desencadenada por un antígeno exógeno conocido (el gluten). Está fuertemente asociada al sistema HLA, aunque otros factores genéticos, ambientales e inmunológicos, aún no completamente identificados, determinarían el momento y forma de presentación. La respuesta inmune en la mucosa intestinal frente a ciertos péptidos derivados de gliadinas es caracterizada por una fuerte respuesta de tipo TH1 (con predominio de IFN¿ secretado por linfocitos T específicos), la que es probablemente precedida por una respuesta inmune innata, mediada fundamentalmente por IL-15. La dieta estricta libre de gluten es la forma más eficaz de revertir las alteraciones de la mucosa intestinal y la sintomatología. Sin embargo, las transgresiones y el bajo cumplimiento de la dieta han conducido a formular nuevas estrategias terapéuticas que se discuten en esta revisión

Enfermedad celíaca. Nuevas perspectivas terapeúticas basadas en un mejor conocimiento de su patogenia molecular

Producción CientíficaLa enfermedad celíaca (EC) es una patología gastrointestinal crónica de tipo autoinmune desencadenada por un antígeno exógeno conocido (el gluten). Está fuertemente asociada al sistema HLA, aunque otros factores genéticos, ambientales e inmunológicos, aún no completamente identificados, determinarían el momento y forma de presentación. La respuesta inmune en la mucosa intestinal frente a ciertos péptidos derivados de gliadinas es caracterizada por una fuerte respuesta de tipo TH1 (con predominio de IFNγ secretado por linfocitos T específicos), la que es probablemente precedida por una respuesta inmune innata, mediada fundamentalmente por IL-15. La dieta estricta libre de gluten es la forma más eficaz de revertir las alteraciones de la mucosa intestinal y la sintomatología. Sin embargo, las transgresiones y el bajo cumplimiento de la dieta han conducido a formular nuevas estrategias terapéuticas que se discuten en esta revisión