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...

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Autores: Hernández Fernaud, Juan Ramón, Papoutsopoulou, Stamatia, Tang, Joseph, Elramli, Ahmed H., Williams, Jonathan M., Gupta, Nitika, Ikuomola, Felix I., Sheibani-Tezerji, Raheleh, Alam, Mohammad T., Caamaño, Jorge H., Probert, Chris S., Muller, Werner, Duckworth, Carrie A., Pritchard, D. Mark
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
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spelling Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosaHernández Fernaud, Juan RamónPapoutsopoulou, StamatiaTang, JosephElramli, Ahmed H.Williams, Jonathan M.Gupta, NitikaIkuomola, Felix I.Sheibani-Tezerji, RahelehAlam, Mohammad T.Caamaño, Jorge H.Probert, Chris S.Muller, WernerDuckworth, Carrie A.Pritchard, D. Markintestinal mucosaimmunoglobulinsplasma cellsNF-κBNfkb2RelBThe 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.Bioquímica, Microbiología, Biología Celular y GenéticaUnidad de Investigación, Hospital Universitario de Canarias.202420242022info:eu-repo/semantics/articleapplication/pdfhttp://riull.ull.es/xmlui/handle/915/38863reponame:RIULL. Repositorio Institucional de la Universidad de La Lagunainstname:Universidad de La Laguna (ULL)InglésAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 323, No. 4Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ESoai:riull.ull.es:915/388632026-06-22T13:13:57Z
dc.title.none.fl_str_mv Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
title Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
spellingShingle Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
Hernández Fernaud, Juan Ramón
intestinal mucosa
immunoglobulins
plasma cells
NF-κB
Nfkb2
RelB
title_short Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
title_full Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
title_fullStr Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
title_full_unstemmed Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
title_sort Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa
dc.creator.none.fl_str_mv Hernández Fernaud, Juan Ramón
Papoutsopoulou, Stamatia
Tang, Joseph
Elramli, Ahmed H.
Williams, Jonathan M.
Gupta, Nitika
Ikuomola, Felix I.
Sheibani-Tezerji, Raheleh
Alam, Mohammad T.
Caamaño, Jorge H.
Probert, Chris S.
Muller, Werner
Duckworth, Carrie A.
Pritchard, D. Mark
author Hernández Fernaud, Juan Ramón
author_facet Hernández Fernaud, Juan Ramón
Papoutsopoulou, Stamatia
Tang, Joseph
Elramli, Ahmed H.
Williams, Jonathan M.
Gupta, Nitika
Ikuomola, Felix I.
Sheibani-Tezerji, Raheleh
Alam, Mohammad T.
Caamaño, Jorge H.
Probert, Chris S.
Muller, Werner
Duckworth, Carrie A.
Pritchard, D. Mark
author_role author
author2 Papoutsopoulou, Stamatia
Tang, Joseph
Elramli, Ahmed H.
Williams, Jonathan M.
Gupta, Nitika
Ikuomola, Felix I.
Sheibani-Tezerji, Raheleh
Alam, Mohammad T.
Caamaño, Jorge H.
Probert, Chris S.
Muller, Werner
Duckworth, Carrie A.
Pritchard, D. Mark
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Bioquímica, Microbiología, Biología Celular y Genética
Unidad de Investigación, Hospital Universitario de Canarias.
dc.subject.none.fl_str_mv intestinal mucosa
immunoglobulins
plasma cells
NF-κB
Nfkb2
RelB
topic intestinal mucosa
immunoglobulins
plasma cells
NF-κB
Nfkb2
RelB
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://riull.ull.es/xmlui/handle/915/38863
url http://riull.ull.es/xmlui/handle/915/38863
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 323, No. 4
dc.rights.none.fl_str_mv Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)
info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES
rights_invalid_str_mv Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:RIULL. Repositorio Institucional de la Universidad de La Laguna
instname:Universidad de La Laguna (ULL)
instname_str Universidad de La Laguna (ULL)
reponame_str RIULL. Repositorio Institucional de la Universidad de La Laguna
collection RIULL. Repositorio Institucional de la Universidad de La Laguna
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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