title: Spontaneous colitis in Muc2-deficient mice reflects clinical and cellular features of active ulcerative colitis.
abstract: BACKGROUND
  The colonic mucus layer plays a critical role in intestinal homeostasis by limiting contact between luminal bacteria and the mucosal immune system. A defective mucus barrier in animal models allows bacterial contact with the intestinal epithelium and results in spontaneous colitis. A defective mucus barrier is also a key feature of active ulcerative colitis (UC). Alterations in the immune compartment due to intestinal bacterial breach in mice lacking the colon mucus barrier have not been characterized and correlated to active UC.
  
  
  OBJECTIVE
  To characterize alterations in the immune compartment due to intestinal bacterial breach in Muc2-/- mice, which lack the colon mucus barrier, and correlate the findings to active UC.
  
  
  METHODS
  Bacterial contact with colon epithelium and penetration into colon tissue was examined in Muc2-/- mice and colon biopsies from patients with active UC using fluorescence microscopy and qPCR. Neutrophils, lymphocytes, CD103+ dendritic cell subsets and macrophages in colon from Muc2-/- mice and biopsies from UC patients were quantitated by flow cytometry.
  
  
  RESULTS
  Inflamed UC patients and Muc2-/- mice had bacteria in contact with the colon epithelium. Bacterial rRNA was present in colonic mucosa in humans and Muc2-/- mice and in the draining lymph nodes of mice. Inflamed Muc2-/- mice and UC patients had elevated colon neutrophils, T cells and macrophages while a reduced frequency of CD103+ DCs was present in the inflamed colon of both mice and humans.
  
  
  CONCLUSIONS
  The parallel features of the colon immune cell compartment in Muc2-/- mice and UC patients supports the usefulness of this model to understand the early phase of spontaneous colitis and will provide insight into novel strategies to treat UC.
authors.affiliation: Department of Microbiology and Immunology and the Mucosal Immunobiology and Vaccine Center (MIVAC), Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ulf A
authors.initials: UA
authors.lastname: Wenzel
authors.affiliation: Department of Microbiology and Immunology and the Mucosal Immunobiology and Vaccine Center (MIVAC), Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and MIVAC, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Magnusson
authors.affiliation: Department of Microbiology and Immunology and the Mucosal Immunobiology and Vaccine Center (MIVAC), Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Rydström
authors.affiliation: Department of Microbiology and Immunology and the Mucosal Immunobiology and Vaccine Center (MIVAC), Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Jonstrand
authors.affiliation: Department of Microbiology and Immunology and the Mucosal Immunobiology and Vaccine Center (MIVAC), Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Julia
authors.initials: J
authors.lastname: Hengst
authors.affiliation: Department of Medical Biochemistry, Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and MIVAC, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Malin E V
authors.initials: ME
authors.lastname: Johansson
authors.affiliation: Department of Oncology, Albert Einstein Cancer Center/Montefiore Medical Center, New York City, New York, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Velcich
authors.affiliation: Department of Microbiology and Immunology and the Mucosal Immunobiology and Vaccine Center (MIVAC), Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and MIVAC, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Öhman
authors.affiliation: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and MIVAC, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Strid
authors.affiliation: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and MIVAC, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Sjövall
authors.affiliation: Department of Medical Biochemistry, Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and MIVAC, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson
authors.affiliation: Department of Microbiology and Immunology and the Mucosal Immunobiology and Vaccine Center (MIVAC), Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Wick
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002452:Cell Count; D003093:Colitis, Ulcerative / Q000382:microbiology / Q000473:pathology*; D003106:Colon / Q000382:microbiology / Q000473:pathology; D003713:Dendritic Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology; D039001:Integrin alpha Chains / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D055262:Mucin-2 / Q000172:deficiency* / Q000378:metabolism; D020556:Neutrophil Infiltration; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D018950:Lipopolysaccharide Receptors; D055262:Mucin-2; C091367:alpha E integrins