دورية أكاديمية
أعرض في EDS

Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice.

التفاصيل البيبلوغرافية
العنوان: Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice.
المؤلفون: Rogala AR; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Department of Pediatrics, Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Schoenborn AA; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Department of Pediatrics, Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Fee BE; Geriatric Research, Education, and Clinical Center, VA Medical Center, Durham, NC 27705, USA., Cantillana VA; Departments of Medicine; Molecular Genetics and Microbiology; and Immunology; Division of Geriatrics, and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC 27710, USA., Joyce MJ; Department of Medicine, Division of Infectious Disease, Duke University Medical Center, Durham, NC 27710, USA., Gharaibeh RZ; Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC 28223, USA., Roy S; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Department of Pediatrics, Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Fodor AA; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC 28223, USA., Sartor RB; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Taylor GA; Geriatric Research, Education, and Clinical Center, VA Medical Center, Durham, NC 27705, USA.; Departments of Medicine; Molecular Genetics and Microbiology; and Immunology; Division of Geriatrics, and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC 27710, USA., Gulati AS; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA ajay_gulati@med.unc.edu.; Department of Pediatrics, Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
المصدر: Disease models & mechanisms [Dis Model Mech] 2018 Feb 07; Vol. 11 (2). Date of Electronic Publication: 2018 Feb 07.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Company of Biologists Ltd Country of Publication: England NLM ID: 101483332 Publication Model: Electronic Cited Medium: Internet ISSN: 1754-8411 (Electronic) Linking ISSN: 17548403 NLM ISO Abbreviation: Dis Model Mech Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge : Company of Biologists Ltd., c2008-
مواضيع طبية MeSH: Environment*, GTP-Binding Proteins/*deficiency , Inflammation/*pathology , Intestines/*pathology , Paneth Cells/*pathology, Animals ; Biodiversity ; Cell Proliferation ; Colitis/microbiology ; Colitis/pathology ; Dextran Sulfate ; Disease Susceptibility ; Epithelial Cells/pathology ; GTP-Binding Proteins/metabolism ; Gastrointestinal Microbiome ; Genotype ; Goblet Cells/pathology ; Helicobacter/physiology ; Inflammation/microbiology ; Intestines/microbiology ; Mice, Knockout ; Paneth Cells/metabolism ; Phenotype ; Specific Pathogen-Free Organisms
مستخلص: Crohn's disease (CD) represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-related GTPase M ( IRGM ) is an established risk allele in CD. We have shown previously that conventionally raised (CV) mice lacking the IRGM ortholog, Irgm1 exhibit abnormal Paneth cells (PCs) and increased susceptibility to intestinal injury. In the present study, we sought to utilize this model system to determine if environmental conditions impact these phenotypes, as is thought to be the case in human CD. To accomplish this, wild-type and Irgm1 -/- mice were rederived into specific pathogen-free (SPF) and germ-free (GF) conditions. We next assessed how these differential housing environments influenced intestinal injury patterns, and epithelial cell morphology and function in wild-type and Irgm1 -/- mice. Remarkably, in contrast to CV mice, SPF Irgm1 -/- mice showed only a slight increase in susceptibility to dextran sodium sulfate-induced inflammation. SPF Irgm1 -/- mice also displayed minimal abnormalities in PC number and morphology, and in antimicrobial peptide expression. Goblet cell numbers and epithelial proliferation were also unaffected by Irgm1 in SPF conditions. No microbial differences were observed between wild-type and Irgm1 -/- mice, but gut bacterial communities differed profoundly between CV and SPF mice. Specifically, Helicobacter sequences were significantly increased in CV mice; however, inoculating SPF Irgm1 -/- mice with Helicobacter hepaticus was not sufficient to transmit a pro-inflammatory phenotype. In summary, our findings suggest the impact of Irgm1-deficiency on susceptibility to intestinal inflammation and epithelial function is critically dependent on environmental influences. This work establishes the importance of Irgm1 -/- mice as a model to elucidate host-environment interactions that regulate mucosal homeostasis and intestinal inflammatory responses. Defining such interactions will be essential for developing novel preventative and therapeutic strategies for human CD.
Competing Interests: Competing interestsThe authors declare no competing or financial interests.
(© 2018. Published by The Company of Biologists Ltd.)
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معلومات مُعتمدة: P01 DK094779 United States DK NIDDK NIH HHS; P40 OD010995 United States OD NIH HHS; P30 DK034987 United States DK NIDDK NIH HHS; K08 DK095917 United States DK NIDDK NIH HHS; R01 AI057831 United States AI NIAID NIH HHS; R03 DK104005 United States DK NIDDK NIH HHS; I01 BX002369 United States BX BLRD VA; T32 DK007737 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: Experimental colitis; Immunity-related GTPases; Inflammatory bowel diseases
المشرفين على المادة: 0 (Ifi1 protein, mouse)
9042-14-2 (Dextran Sulfate)
EC 3.6.1.- (GTP-Binding Proteins)
تواريخ الأحداث: Date Created: 20180124 Date Completed: 20181001 Latest Revision: 20210618
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5894938
DOI: 10.1242/dmm.031070
PMID: 29361512
قاعدة البيانات: MEDLINE
الوصف
تدمد:1754-8411
DOI:10.1242/dmm.031070