Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa

Papoutsopoulou, Stamatia ORCID: 0000-0001-6665-8508, Tang, Joseph, Elramli, Ahmed H, Williams, Jonathan M, Gupta, Nitika ORCID: 0000-0003-3885-2500, Ikuomola, Felix I, Sheibani-Tezerji, Raheleh, Alam, Mohammad T, Hernandez-Fernaud, Juan R, Caamano, Jorge H
et al (show 4 more authors) (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, 323 (4). G306-G317.

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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.

Item Type: Article
Uncontrolled Keywords: immunoglobulins, intestinal mucosa, NF-KB, Nfkb2, plasma cells, RelB
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 18 Oct 2022 14:30
Last Modified: 27 Nov 2023 13:19
DOI: 10.1152/ajpgi.00037.2022
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