| Title: |
Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa. |
| Authors: |
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, Werner; Pritchard, DM |
| Source: |
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.00037.2022 |
| Publication Year: |
2022 |
| Collection: |
The University of Manchester: Research Explorer - Publications |
| Subject Terms: |
NF-κB; Nfkb2; RelB; immunoglobulins; intestinal mucosa; plasma cells; Lipopolysaccharides/pharmacology; NF-kappa B p52 Subunit/genetics; Immunoglobulins/metabolism; Immunoglobulin A/metabolism; Plasma Cells/metabolism; Animals; Intestinal Mucosa/metabolism; Proteomics; Mice; NF-kappa B/metabolism; ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation; name=Lydia Becker Institute |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0193-1857; 1522-1547 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35916405; info:eu-repo/semantics/altIdentifier/pissn/0193-1857; info:eu-repo/semantics/altIdentifier/eissn/1522-1547 |
| DOI: |
10.1152/ajpgi.00037.2022 |
| Availability: |
https://research.manchester.ac.uk/en/publications/1b68d0f0-f804-431c-a657-c50bdee95f53; https://doi.org/10.1152/ajpgi.00037.2022; http://europepmc.org/abstract/med/35916405; https://www.scopus.com/pages/publications/85138443750; https://www.mendeley.com/catalogue/ebfcee1a-e6cb-33af-9332-a0a9155f98ea/ |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.C55BCAFF |
| Database: |
BASE |