دورية أكاديمية
Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
| العنوان: | Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa |
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| المؤلفون: | Papoutsopoulou S., Tang J., Elramli A.H., Williams J.M., Gupta N., Ikuomola F.I., Sheibani-Tezerji R., Alam M.T., Hernández-Fernaud J.R., Caamaño J.H., Probert C.S., Muller W., Duckworth C.A., Mark Pritchard D. |
| المصدر: | American Journal of Physiology - Gastrointestinal and Liver Physiology ; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85138443750&doi=10.1152%2fajpgi.00037.2022&partnerID=40&md5=9e2d389e9bfc1433da9bc6af8f6b815eTest |
| سنة النشر: | 2022 |
| المجموعة: | University of Thessaly Institutional Repository / Ιδρυματικό Αποθετήριο Πανεπιστημίου Θεσσαλίας |
| مصطلحات موضوعية: | immunoglobulin, immunoglobulin A, immunoglobulin enhancer binding protein, immunoglobulin M, lipopolysaccharide, protein p52, syndecan 1, transcription factor RelB, Nfkb2 protein, mouse, adult, animal cell, animal experiment, animal model, animal tissue, apoptosis, Article, B lymphocyte, cell differentiation, controlled study, enzyme linked immunosorbent assay, high throughput sequencing, immunoglobulin blood level, immunohistochemistry, intestine villus, male, nonhuman, plasma cell, protein expression, proteomics |
| الوصف: | The alternative (noncanonical) nuclear factor-κB (NF-κB) signaling pathway predominantly regulates the function of the p52/RelB heterodimer. Germline Nfkb2 deficiency in mice leads to loss of p100/p52 protein and offers protection against a variety of gastrointestinal conditions, including azoxymethane/dextran sulfate sodium (DSS)-induced colitis-associated cancer and lipopolysaccharide (LPS)induced small intestinal epithelial apoptosis. However, the common underlying protective mechanisms have not yet been fully elucidated. We applied high-throughput RNA-Seq and proteomic analyses to characterize the transcriptional and protein signatures of the small intestinal mucosa of naïve adult Nfkb2-/- mice. Those data were validated by immunohistochemistry and quantitative ELISA using both small intestinal tissue lysates and serum. We identified a B-lymphocyte defect as a major transcriptional signature in the small intestinal mucosa and immunoglobulin A as the most downregulated protein by proteomic analysis in Nfkb2-/- mice. Small intestinal immunoglobulins were dramatically dysregulated, with undetectable levels of immunoglobulin A and greatly increased amounts of immunoglobulin M being detected. The numbers of IgA-producing, cluster of differentiation (CD)138-positive plasma cells were also reduced in the lamina propria of the small intestinal villi of Nfkb2/-/- mice. This phenotype was even more striking in the small intestinal mucosa of RelB-/- mice, although these mice were equally sensitive to LPS-induced intestinal apoptosis as their RelB+/+ wild-type counterparts. NF-κB2/p52 deficiency confers resistance to LPS-induced small intestinal apoptosis and also appears to regulate the plasma cell population and immunoglobulin levels within the gut. Copyright © 2022 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 01931857 |
| العلاقة: | http://hdl.handle.net/11615/77906Test |
| DOI: | 10.1152/ajpgi.00037.2022 |
| الإتاحة: | https://doi.org/10.1152/ajpgi.00037.2022Test http://hdl.handle.net/11615/77906Test |
| رقم الانضمام: | edsbas.485D0444 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 01931857 |
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| DOI: | 10.1152/ajpgi.00037.2022 |