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Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
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Papoutsopoulou, Stamatia, Tang, Joseph, Elramli, Ahmed H., Williams, Jonathan M., Gupta, Nitika, Ikuomola, Felix I., Sheibani-Tezerji, Raheleh, Alam, Mohammad T., Hernandez-Fernaud, Juan Ramon, Caamano, Jorge H., Probert, Chris S., Muller, Werner, Duckworth, Carrie A. and Pritchard, D. Mark (2022) Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa. Gastrointestinal and Liver Physiology, 323 (4). G306-G317. doi:10.1152/ajpgi.00037.2022 ISSN 0193-1857.
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WRAP-Nfkb2deficiency-impact-plasma-cells-immunoglobuline-murine-small-22.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2312Kb) | Preview |
Official URL: http://dx.doi.org/10.1152/ajpgi.00037.2022
Abstract
Background & Aims: The alternative (non-canonical) nuclear factor-kB (NF-kB) signalling 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. Methods: We applied high throughput RNASeq and proteomic analyses to characterise 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. Results: 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, CD138+ve 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. Conclusions: NF-kB2/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.
| Item Type: | Journal Article | ||||||||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||||||
| Journal or Publication Title: | Gastrointestinal and Liver Physiology | ||||||||||
| Publisher: | American Physiological Society | ||||||||||
| ISSN: | 0193-1857 | ||||||||||
| Official Date: | 1 October 2022 | ||||||||||
| Dates: |
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| Volume: | 323 | ||||||||||
| Number: | 4 | ||||||||||
| Page Range: | G306-G317 | ||||||||||
| DOI: | 10.1152/ajpgi.00037.2022 | ||||||||||
| Status: | Peer Reviewed | ||||||||||
| Publication Status: | Published | ||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||
| Copyright Holders: | American Journal of Physiology-Gastrointestinal and Liver Physiology | ||||||||||
| Date of first compliant deposit: | 25 October 2022 | ||||||||||
| Date of first compliant Open Access: | 25 October 2022 |
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