RT info:eu-repo/semantics/article
T1 Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
A1 Hernández Fernaud, Juan Ramón
A1 Papoutsopoulou, Stamatia
A1 Tang, Joseph
A1 Elramli, Ahmed H.
A1 Williams, Jonathan M.
A1 Gupta, Nitika
A1 Ikuomola, Felix I.
A1 Sheibani-Tezerji, Raheleh
A1 Alam, Mohammad T.
A1 Caamaño, Jorge H.
A1 Probert, Chris S.
A1 Muller, Werner
A1 Duckworth, Carrie A.
A1 Pritchard, D. Mark
A2 BioquímicaMicrobiología, Biología Celular y Genética
A2 Unidad de InvestigaciónHospital Universitario de Canarias.
K1 intestinal mucosa
K1 immunoglobulins
K1 plasma cells
K1 NF-κB
K1 Nfkb2
K1 RelB
AB 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.
YR 2022
FD 2022
LK http://riull.ull.es/xmlui/handle/915/38863
UL http://riull.ull.es/xmlui/handle/915/38863
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 19-oct-2024