دورية أكاديمية
Goblet Cell Derived RELM-β Recruits CD4+ T Cells during Infectious Colitis to Promote Protective Intestinal Epithelial Cell Proliferation.
العنوان: | Goblet Cell Derived RELM-β Recruits CD4+ T Cells during Infectious Colitis to Promote Protective Intestinal Epithelial Cell Proliferation. |
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المؤلفون: | Bergstrom KS; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada., Morampudi V; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada., Chan JM; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada., Bhinder G; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada., Lau J; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada., Yang H; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada., Ma C; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada., Huang T; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada., Ryz N; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada., Sham HP; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada., Zarepour M; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada., Zaph C; Biomedical Research Centre, University of British Columbia, Vancouver, Canada., Artis D; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford Weill Department of Medicine, West Cornell Medical College, Cornell University, New York, New York, United States of America., Nair M; Division of Biomedical Sciences, University of California, Riverside, Riverside, California, United States of America., Vallance BA; Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, Vancouver, Canada. |
المصدر: | PLoS pathogens [PLoS Pathog] 2015 Aug 18; Vol. 11 (8), pp. e1005108. Date of Electronic Publication: 2015 Aug 18 (Print Publication: 2015). |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science, c2005- |
مواضيع طبية MeSH: | Cell Proliferation*, CD4-Positive T-Lymphocytes/*immunology , Colitis/*immunology , Goblet Cells/*immunology , Hormones, Ectopic/*immunology , Intestinal Mucosa/*immunology, Animals ; Cell Separation ; Citrobacter rodentium ; Colitis/metabolism ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Fluorescent Antibody Technique ; Goblet Cells/metabolism ; Hormones, Ectopic/metabolism ; Intercellular Signaling Peptides and Proteins ; Intestinal Mucosa/microbiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Polymerase Chain Reaction |
مستخلص: | Enterohemorrhagic Escherichia coli and related food and waterborne pathogens pose significant threats to human health. These attaching/effacing microbes infect the apical surface of intestinal epithelial cells (IEC), causing severe diarrheal disease. Colonizing the intestinal luminal surface helps segregate these microbes from most host inflammatory responses. Based on studies using Citrobacter rodentium, a related mouse pathogen, we speculate that hosts rely on immune-mediated changes in IEC, including goblet cells to defend against these pathogens. These changes include a CD4+ T cell-dependent increase in IEC proliferation to replace infected IEC, as well as altered production of the goblet cell-derived mucin Muc2. Another goblet cell mediator, REsistin-Like Molecule (RELM)-β is strongly induced within goblet cells during C. rodentium infection, and was detected in the stool as well as serum. Despite its dramatic induction, RELM-β's role in host defense is unclear. Thus, wildtype and RELM-β gene deficient mice (Retnlb-/-) were orally infected with C. rodentium. While their C. rodentium burdens were only modestly elevated, infected Retnlb-/- mice suffered increased mortality and mucosal ulceration due to deep pathogen penetration of colonic crypts. Immunostaining for Ki67 and BrDU revealed Retnlb-/- mice were significantly impaired in infection-induced IEC hyper-proliferation. Interestingly, exposure to RELM-β did not directly increase IEC proliferation, rather RELM-β acted as a CD4+ T cell chemoattractant. Correspondingly, Retnlb-/- mice showed impaired CD4+ T cell recruitment to their infected colons, along with reduced production of interleukin (IL)-22, a multifunctional cytokine that directly increased IEC proliferation. Enema delivery of RELM-β to Retnlb-/- mice restored CD4+ T cell recruitment, concurrently increasing IL-22 levels and IEC proliferation, while reducing mucosal pathology. These findings demonstrate that RELM-β and goblet cells play an unexpected, yet critical role in recruiting CD4+ T cells to the colon to protect against an enteric pathogen, in part via the induction of increased IEC proliferation. |
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معلومات مُعتمدة: | R01 AI091759 United States AI NIAID NIH HHS; Canada Canadian Institutes of Health Research |
المشرفين على المادة: | 0 (Hormones, Ectopic) 0 (Intercellular Signaling Peptides and Proteins) 0 (Retnlb protein, mouse) |
تواريخ الأحداث: | Date Created: 20150819 Date Completed: 20160503 Latest Revision: 20201209 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC4540480 |
DOI: | 10.1371/journal.ppat.1005108 |
PMID: | 26285214 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1553-7374 |
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DOI: | 10.1371/journal.ppat.1005108 |