IL-22-STAT3 Pathway Plays a Key Role in the Maintenance of Ileal Homeostasis in Mice Lacking Secreted Mucus Barrier

Autor: Bruno Sovran, Jan P. Dekker, Peng Lu, Ingrid B. Renes, Paul de Vos, Floor Hugenholtz, Ellen H. Stolte, Michiel Kleerebezem, Peter van Baarlen, Linda M. P. Loonen, Jerry M. Wells, Mark V. Boekschoten, Clara Belzer
Přispěvatelé: Man, Biomaterials and Microbes (MBM), Translational Immunology Groningen (TRIGR), Pediatrics, Academic Medical Center
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Chemokine
Apoptosis
Interleukin 22
Transcriptome
Immunoenzyme Techniques
STAT3
Voeding
Metabolisme en Genomica
Mice
Microbiologie
Immunology and Allergy
Homeostasis
COLONIC GENE-EXPRESSION
bacteria
Defensin
Cells
Cultured
In Situ Hybridization
Fluorescence
Oligonucleotide Array Sequence Analysis
Mice
Knockout
biology
EXPERIMENTAL COLITIS
MUC2-DEFICIENT MICE
Reverse Transcriptase Polymerase Chain Reaction
Gastroenterology
intestinal homeostasis
respiratory system
PANCREATITIS-ASSOCIATED PROTEIN
MICROBIOTA
Metabolism and Genomics
Cell biology
muc2-deficient mice
medicine.anatomical_structure
Metabolisme en Genomica
BACTERIA
Nutrition
Metabolism and Genomics
ileum
Signal transduction
Signal Transduction
STAT3 Transcription Factor
pancreatitis-associated protein
MUCIN MUC2
experimental colitis
Blotting
Western
Ileum
Real-Time Polymerase Chain Reaction
Microbiology
digestive system
stat3
Voeding
Downregulation and upregulation
colonic gene-expression
mucin muc2
medicine
microbiota
Animals
Host-Microbe Interactomics
RNA
Messenger
interleukin 22
Nutrition
Cell Proliferation
Mucin-2
inflammatory-bowel-disease
Gene Expression Profiling
Interleukins
Mucus
digestive system diseases
Reg3 proteins
Immunology
Muc2
biology.protein
WIAS
INTESTINAL EPITHELIAL-CELLS
intestinal epithelial-cells
INFLAMMATORY-BOWEL-DISEASE
Zdroj: Inflammatory Bowel Diseases, 21(3), 531-542. LIPPINCOTT WILLIAMS & WILKINS
Inflammatory Bowel Diseases 21 (2015) 3
Inflammatory Bowel Diseases, 21(3), 531-542
Inflammatory Bowel Diseases, 21(3), 531-542. Oxford University Press
Inflammatory bowel diseases, 21(3), 531-542. John Wiley and Sons Inc.
ISSN: 1078-0998
Popis: Background:Muc2-deficient mice show no signs of ileal pathology but the mechanisms remained unknown.Methods:Wild-type (WT), Muc2(+/-), and Muc2(-/-) mice were killed at 2, 4, and 8 weeks of age. Total RNA from ileum was used for full genome transcriptome analysis and qPCR. Microbiota composition was determined using a mouse intestinal chip (MITChip). Morphological and immunohistological studies were performed on segments of ileum.Results:The ileum was colonized by more diverse microbiota in young (week 4) WT than in Muc2(-/-) mice, and composition was influenced by genotype. Weaning was associated with major changes in the transcriptome of all mice, and the highest number of differentially expressed genes compared with adults, reflecting temporal changes in microbiota. Although the spatial compartmentalization of bacteria was compromised in Muc2(-/-) mice, gene set enrichment analysis revealed a downregulation of Toll-like receptor, immune, and chemokine signaling pathways compared to WT mice. The predicted effects of enhanced IL-22 signaling were identified in the Muc2(-/-) transcriptome as the upregulation of epithelial cell proliferation altered expression of mitosis and cell-cycle control pathways. This is consistent with increased villus length and number of Ki67(+) epithelial cells in Muc2(-/-) mice. Additionally, expression of the network of IL-22 regulated defense genes, including Fut2, Reg3, Reg3, Relmb, and the Defensin Defb46 were increased in Muc2(-/-) mice.Conclusions:These findings highlight a role for the IL-22-STAT3 pathway in maintaining ileal homeostasis when the mucus barrier is compromised and its potential as a target for novel therapeutic strategies in inflammatory bowel disease.
Databáze: OpenAIRE
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