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Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis
Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
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2012 (English)In: Immunity, ISSN 1074-7613, E-ISSN 1097-4180, Vol. 37, no 3, p. 563-573Article in journal (Refereed) Published
Abstract [en]

Mice lacking junctional adhesion molecule A (JAM-A, encoded by F11r) exhibit enhanced intestinal epithelial permeability, bacterial translocation, and elevated colonic lymphocyte numbers, yet do not develop colitis. To investigate the contribution of adaptive immune compensation in response to increased intestinal epithelial permeability, we examined the susceptibility of F11r(-/-)Rag1(-/-) mice to acute colitis. Although negligible contributions of adaptive immunity in F11r(+/+)Rag1(-/-) mice were observed, F11r(-/-)Rag1(-/-) mice exhibited increased microflora-dependent colitis. Elimination of T cell subsets and cytokine analyses revealed a protective role for TGF-beta-producing CD4(+) T cells in F11r(-/-) mice. Additionally, loss of JAM-A resulted in elevated mucosal and serum IgA that was dependent upon CD4(+) T cells and TGF-beta. Absence of IgA in F11r(+/+)Igha(-/-) mice did not affect disease, whereas F11r(-/-)Igha(-/-) mice displayed markedly increased susceptibility to acute injury-induced colitis. These data establish a role for adaptive immune-mediated protection from acute colitis under conditions of intestinal epithelial barrier compromise.

Place, publisher, year, edition, pages
Cambridge, United States: Cell Press , 2012. Vol. 37, no 3, p. 563-573
Keywords [en]
Adaptive Immunity/genetics/*immunology, Animals, Bacterial Translocation/genetics/immunology, CD4-Positive T-Lymphocytes/immunology/metabolism, Cell Adhesion Molecules/genetics/immunology, Colitis/chemically induced/genetics/*immunology, Dextran Sulfate, Epithelium/immunology/metabolism, Female, Flow Cytometry, Gene Expression, Homeodomain Proteins/genetics/immunology, Immunoglobulin A/genetics/immunology, Intestinal Mucosa/*immunology/metabolism/microbiology, Intestines/*immunology/metabolism/microbiology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Permeability, Receptors, Cell Surface/genetics/immunology, Reverse Transcriptase Polymerase Chain Reaction, Transforming Growth Factor beta/genetics/immunology/metabolism
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-141654DOI: 10.1016/j.immuni.2012.06.017ISI: 000309199000019PubMedID: 22981539Scopus ID: 2-s2.0-84866523733ISBN: 1097-4180 (Electronic) 1074-7613 (Linking) OAI: oai:DiVA.org:liu-141654DiVA, id: diva2:1149718
Note

Khounlotham, Manirath Kim, Wooki Peatman, Eric Nava, Porfirio Medina-Contreras, Oscar Addis, Caroline Koch, Stefan Fournier, Benedicte Nusrat, Asma Denning, Timothy L Parkos, Charles A eng R29 DK055679/DK/NIDDK NIH HHS/ K99 AA017870/AA/NIAAA NIH HHS/ DK72564/DK/NIDDK NIH HHS/ DK061379/DK/NIDDK NIH HHS/ DK 064399/DK/NIDDK NIH HHS/ R01 DK072564/DK/NIDDK NIH HHS/ R24 DK064399/DK/NIDDK NIH HHS/ AA017870/AA/NIAAA NIH HHS/ DK59888/DK/NIDDK NIH HHS/ DK055679/DK/NIDDK NIH HHS/ R01 DK055679/DK/NIDDK NIH HHS/ R00 AA017870/AA/NIAAA NIH HHS/ R01 DK061379/DK/NIDDK NIH HHS/ R01 DK059888/DK/NIDDK NIH HHS/ R21 AI083554/AI/NIAID NIH HHS/ AI083554/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2012/09/18 06:00 Immunity. 2012 Sep 21;37(3):563-73. doi: 10.1016/j.immuni.2012.06.017. Epub 2012 Sep 13.

Available from: 2017-10-16 Created: 2017-10-16 Last updated: 2018-01-13Bibliographically approved

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