Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
The alternative (noncanonical) nuclear factor-κB(NF-κB) signaling pathway predominantly regulates the function of the p52/RelB heterodimer. Germline Nfkb2deficiency in mice leads to loss of p100/p52 protein and offers protection against a variety of gastrointestinal conditions, including azoxymethan...
| Autores: | , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de La Laguna (ULL) |
| Repositorio: | RIULL. Repositorio Institucional de la Universidad de La Laguna |
| OAI Identifier: | oai:riull.ull.es:915/38863 |
| Acceso en línea: | http://riull.ull.es/xmlui/handle/915/38863 |
| Access Level: | acceso abierto |
| Palabra clave: | intestinal mucosa immunoglobulins plasma cells NF-κB Nfkb2 RelB |
| Sumario: | The alternative (noncanonical) nuclear factor-κB(NF-κB) signaling pathway predominantly regulates the function of the p52/RelB heterodimer. Germline Nfkb2deficiency 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 RelBþ/þ 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. |
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