Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis
| Autor: | Caroline Addis, Timothy L. Denning, Eric Peatman, Manirath Khounlotham, Charles A. Parkos, Stefan Koch, Asma Nusrat, Oscar Medina-Contreras, Wooki Kim, Porfirio Nava, Bénédicte Fournier |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Immunoglobulin A
CD4-Positive T-Lymphocytes Male medicine.medical_treatment Immunology Gene Expression Receptors Cell Surface Adaptive Immunity Article Epithelium Permeability Mice Immune system Intestinal mucosa Transforming Growth Factor beta medicine Immunology and Allergy Animals Colitis Intestinal Mucosa Receptor Acute colitis Homeodomain Proteins Mice Knockout biology Reverse Transcriptase Polymerase Chain Reaction Dextran Sulfate Acquired immune system medicine.disease Flow Cytometry Molecular biology Intestines Mice Inbred C57BL Cytokine Infectious Diseases Bacterial Translocation biology.protein Female Cell Adhesion Molecules |
| Popis: | Summary 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-β-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-β. 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. |
| Databáze: | OpenAIRE |
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