B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF

Abstract We have previously reported evidence that Nogo-A activation of Nogo-receptor 1 (NgR1) can drive axonal dystrophy during the neurological progression of experimental autoimmune encephalomyelitis (EAE). However, the B-cell activating factor (BAFF/BlyS) may also be an important ligand of NgR d...

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Autores principales: Maha M. Bakhuraysah, Paschalis Theotokis, Jae Young Lee, Amani A. Alrehaili, Pei-Mun Aui, William A. Figgett, Michael F. Azari, John-Paul Abou-Afech, Fabienne Mackay, Christopher Siatskas, Frank Alderuccio, Stephen M. Strittmatter, Nikolaos Grigoriadis, Steven Petratos
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/7f98d0d0bafb467bb50ba3cdc0460e71
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spelling oai:doaj.org-article:7f98d0d0bafb467bb50ba3cdc0460e712021-12-02T14:06:56ZB-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF10.1038/s41598-021-82346-62045-2322https://doaj.org/article/7f98d0d0bafb467bb50ba3cdc0460e712021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82346-6https://doaj.org/toc/2045-2322Abstract We have previously reported evidence that Nogo-A activation of Nogo-receptor 1 (NgR1) can drive axonal dystrophy during the neurological progression of experimental autoimmune encephalomyelitis (EAE). However, the B-cell activating factor (BAFF/BlyS) may also be an important ligand of NgR during neuroinflammation. In the current study we define that NgR1 and its homologs may contribute to immune cell signaling during EAE. Meningeal B-cells expressing NgR1 and NgR3 were identified within the lumbosacral spinal cords of ngr1 +/+ EAE-induced mice at clinical score 1. Furthermore, increased secretion of immunoglobulins that bound to central nervous system myelin were shown to be generated from isolated NgR1- and NgR3-expressing B-cells of ngr1 +/+ EAE-induced mice. In vitro BAFF stimulation of NgR1- and NgR3-expressing B cells, directed them into the cell cycle DNA synthesis phase. However, when we antagonized BAFF signaling by co-incubation with recombinant BAFF-R, NgR1-Fc, or NgR3 peptides, the B cells remained in the G0/G1 phase. The data suggest that B cells express NgR1 and NgR3 during EAE, being localized to infiltrates of the meninges and that their regulation is governed by BAFF signaling.Maha M. BakhuraysahPaschalis TheotokisJae Young LeeAmani A. AlrehailiPei-Mun AuiWilliam A. FiggettMichael F. AzariJohn-Paul Abou-AfechFabienne MackayChristopher SiatskasFrank AlderuccioStephen M. StrittmatterNikolaos GrigoriadisSteven PetratosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Maha M. Bakhuraysah
Paschalis Theotokis
Jae Young Lee
Amani A. Alrehaili
Pei-Mun Aui
William A. Figgett
Michael F. Azari
John-Paul Abou-Afech
Fabienne Mackay
Christopher Siatskas
Frank Alderuccio
Stephen M. Strittmatter
Nikolaos Grigoriadis
Steven Petratos
B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
description Abstract We have previously reported evidence that Nogo-A activation of Nogo-receptor 1 (NgR1) can drive axonal dystrophy during the neurological progression of experimental autoimmune encephalomyelitis (EAE). However, the B-cell activating factor (BAFF/BlyS) may also be an important ligand of NgR during neuroinflammation. In the current study we define that NgR1 and its homologs may contribute to immune cell signaling during EAE. Meningeal B-cells expressing NgR1 and NgR3 were identified within the lumbosacral spinal cords of ngr1 +/+ EAE-induced mice at clinical score 1. Furthermore, increased secretion of immunoglobulins that bound to central nervous system myelin were shown to be generated from isolated NgR1- and NgR3-expressing B-cells of ngr1 +/+ EAE-induced mice. In vitro BAFF stimulation of NgR1- and NgR3-expressing B cells, directed them into the cell cycle DNA synthesis phase. However, when we antagonized BAFF signaling by co-incubation with recombinant BAFF-R, NgR1-Fc, or NgR3 peptides, the B cells remained in the G0/G1 phase. The data suggest that B cells express NgR1 and NgR3 during EAE, being localized to infiltrates of the meninges and that their regulation is governed by BAFF signaling.
format article
author Maha M. Bakhuraysah
Paschalis Theotokis
Jae Young Lee
Amani A. Alrehaili
Pei-Mun Aui
William A. Figgett
Michael F. Azari
John-Paul Abou-Afech
Fabienne Mackay
Christopher Siatskas
Frank Alderuccio
Stephen M. Strittmatter
Nikolaos Grigoriadis
Steven Petratos
author_facet Maha M. Bakhuraysah
Paschalis Theotokis
Jae Young Lee
Amani A. Alrehaili
Pei-Mun Aui
William A. Figgett
Michael F. Azari
John-Paul Abou-Afech
Fabienne Mackay
Christopher Siatskas
Frank Alderuccio
Stephen M. Strittmatter
Nikolaos Grigoriadis
Steven Petratos
author_sort Maha M. Bakhuraysah
title B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
title_short B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
title_full B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
title_fullStr B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
title_full_unstemmed B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
title_sort b-cells expressing ngr1 and ngr3 are localized to eae-induced inflammatory infiltrates and are stimulated by baff
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/7f98d0d0bafb467bb50ba3cdc0460e71
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