Abnormal organogenesis of Peyer's patches in mice deficient for NF-κB1, NF-κB2, and Bcl-3
| Autor: | Roland M. Schmid, Monika Wilda, Klaus Pfeffer, Guido Adler, Heidrun Merkle, M Riemann, Horst Hameister, Stephan Paxian, Susanne Liptay |
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| Rok vydání: | 2002 |
| Předmět: |
Receptors
CCR6 Chemokine Gut-associated lymphoid tissue High endothelial venules Gene Expression Immunoglobulins In situ hybridization Biology Mice Peyer's Patches Mucoproteins NF-kappa B p52 Subunit B-Cell Lymphoma 3 Protein Proto-Oncogene Proteins medicine Animals Lymphocytes Macrophage inflammatory protein Adaptor Proteins Signal Transducing Mice Knockout Chemokine CCL20 Hepatology Follicular dendritic cells NF-kappa B Gastroenterology Germinal center Peyer's patch Dendritic Cells Macrophage Inflammatory Proteins Germinal Center Chemokine CXCL13 Molecular biology medicine.anatomical_structure Chemokines CC Mutation Immunology Trans-Activators biology.protein Receptors Chemokine Cell Adhesion Molecules Chemokines CXC Transcription Factors |
| Zdroj: | Gastroenterology. 122:1853-1868 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/gast.2002.33651 |
| Popis: | Background & Aims: Nuclear factor (NF) κB1, NF-κB2, and Bcl-3 encode for proteins of the NF-κB/Rel/IκB families, known as regulators of innate and adoptive immune responses. Targeted disruption of these genes showed essential roles in lymphoid organ development and organization. Methods: NF-κB1–, NF-κB2–, and Bcl-3–deficient mouse lines were established, and their role in organogenesis of Peyer's patches (PP) was investigated. Results: Macroscopic inspection showed a reduced number and size of PP in Bcl-3 −/− and NF-κB1 −/− mice but failed to detect PP in NF-κB2 −/− mice. Whole-mount in situ hybridization revealed the presence of interleukin-7 receptor–α spots in NF-κB2 −/− mice, indicating no defect in PP organogenesis of NF-κB2 −/− mice in principle. Immunostaining shows that residual lymphocytes mainly consist of T cells. B cells are substantially reduced and are accumulated as terminal extravasations. Organized follicular structures and follicular dendritic cell networks fail to form, and myeloid, but not lymphoid, dendritic cells are obviously reduced. Expression of the chemokines macrophage inflammatory protein-3α, B-lymphocyte chemoattractant, and thymus-expressed chemokine is impaired in epithelial cells and in the subendothelial dome area that is not well defined. A similar but less severe phenotype is seen in Bcl-3 −/− mice, which also do not develop germinal centers. In contrast, in NF-κB1 −/− mice, T-cell numbers are visibly reduced, and no alteration could be observed in the B-cell and dendritic-cell populations. Conclusions: These data show that all 3 genes are crucial for PP development but contribute differently to PP organogenesis. GASTROENTEROLOGY 2002;122:1853-1868 |
| Databáze: | OpenAIRE |
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