The absence of interleukin 10 affects the morphology, differentiation, granule content and the production of cryptidin-4 in Paneth cells in mice
Autoři:
Loni Berkowitz aff001; Catalina Pardo-Roa aff002; Gigliola Ramírez aff001; Omar P. Vallejos aff002; Valentina P. Sebastián aff002; Claudia A. Riedel aff003; Manuel Álvarez-Lobos aff001; Susan M. Bueno aff002
Působiště autorů:
Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
aff001; Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
aff002; Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias de la Vida, Departamento de Ciencias Biológicas, Universidad Andrés Bello, Santiago, Chile
aff003
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0221618
Souhrn
Paneth cells (PCs) are specialized epithelial cells of the small bowel that contain multiple secretory granules filled with antimicrobial peptides and trophic factors, which are essential for the control of the microorganisms growth and maintaining intestinal integrity. Alterations in their function are associated with an imbalance of the normal microbiota, gastrointestinal infections and inflammatory processes, such as Crohn’s disease (CD). One of the most common murine models for studying CD is IL-10-/- mouse. IL-10-/- mice when housed in conventional conditions and take contact with commensal microorganisms develop an acute enterocolitis mediated by a Th1 immune response. Even though, alterations in PCs function are related to CD, they had not been characterized yet in this mouse model. Here we show that in specific pathogen free conditions IL-10-/- mice have aberrant granules and a large number of immature PCs at the bottom of the crypt in the ileum of IL-10-/- mice before developing intestinal inflammation, along with a reduced expression of Indian Hedgehog. In addition, IL-10-/- Paneth cells presented a reduced expression of cryptidin-4, and a heterogeneous distribution of lysozyme+ granules. The alterations in the maturation of the PCs at the bottom of the crypt were not modified after the colonization by the conventional microbiota. On the other hand, depletion of microbiota altered the phenotype, but did not normalize PCs. Our results suggest that IL-10 could be necessary for the integrity of PCs. Moreover, our results help to explain why IL-10-/- mice develop enterocolitis in response to microorganisms.
Klíčová slova:
Biology and life sciences – Microbiology – Medical microbiology – Microbiome – Microbial genomics – Genetics – Genomics – Anatomy – Digestive system – Gastrointestinal tract – Ileum – Biological tissue – Epithelium – Paneth cells – Developmental biology – Cell differentiation – Cell biology – Cellular types – Animal cells – Epithelial cells – Biochemistry – Enzymology – Enzymes – Lysozyme – Proteins – Medicine and health sciences – Immunology – Immune response – Inflammation – Diagnostic medicine – Signs and symptoms – Pathology and laboratory medicine – Gastroenterology and hepatology – Inflammatory bowel disease
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PLOS One
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