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 |
|---|---|
| المؤلفون: | Stamatia Papoutsopoulou, Joseph Tang, Ahmed H. Elramli, Jonathan M. Williams, Nitika Gupta, Felix I. Ikuomola, Raheleh Sheibani-Tezerji, Mohammad T. Alam, Juan R. Hernández-Fernaud, Jorge H. Caamaño, Chris S. Probert, Werner Muller, Carrie A. Duckworth, D. Mark Pritchard |
| المصدر: | Papoutsopoulou, S, Tang, J, Elramli, AH, Williams, JM, Gupta, N, Ikuomola, FI, Sheibani-Tezerji, R, Alam, MT, Hernández-Fernaud, JR, Caamano, JH, Probert, CS, Muller, W & Pritchard, DM 2022, ' Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa. ', American journal of physiology. Gastrointestinal and liver physiology, vol. 323, no. 4, pp. G306-G317 . https://doi.org/10.1152/ajpgi.00037.2022Test |
| بيانات النشر: | American Physiological Society, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Lipopolysaccharides, Proteomics, Lydia Becker Institute, Physiology, Plasma Cells, immunoglobulins, Immunoglobulins, RelB, Immunoglobulin A/metabolism, NF-kappa B p52 Subunit/genetics, NF-κB, plasma cells, Mice, Nfkb2, NF-kappa B p52 Subunit, ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation, Physiology (medical), Animals, Intestinal Mucosa, Immunoglobulins/metabolism, Hepatology, Plasma Cells/metabolism, NF-kappa B, Gastroenterology, Lipopolysaccharides/pharmacology, Immunoglobulin A, intestinal mucosa, NF-kappa B/metabolism, Intestinal Mucosa/metabolism |
| الوصف: | The alternative (noncanonical) nuclear factor-κB (NF-κB) signaling pathway predominantly regulates the function of the p52/RelB heterodimer. GermlineiNfkb/i2 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 adultiNfkb2/isup-/-/supmice. 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 iniNfkb2/isup-/-/supmice. 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 ofiNfkb2/isup-/-/supmice. This phenotype was even more striking in the small intestinal mucosa ofiRelB/isup-/-/supmice, although these mice were equally sensitive to LPS-induced intestinal apoptosis as theiriRelB/isup+/+/supwild-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.bNEWamp; NOTEWORTHY/bNovel transcriptomic analysis of murine proximal intestinal mucosa revealed an unexpected B cell signature iniNfkb2/isup-/-/supmice. In-depth analysis revealed a defect in the CD38+ B cell population and a gut-specific dysregulation of immunoglobulin levels. |
| تدمد: | 1522-1547 0193-1857 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::433d5bde47aa44c9775813329da986e2Test https://doi.org/10.1152/ajpgi.00037.2022Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....433d5bde47aa44c9775813329da986e2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221547 01931857 |
|---|