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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-82346-6 |
| _version_ | 1818843053188710400 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T04:51:45Z |
| format | Article |
| id | doaj.art-7f98d0d0bafb467bb50ba3cdc0460e71 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:51:45Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7f98d0d0bafb467bb50ba3cdc0460e712022-12-21T20:35:20ZengNature PortfolioScientific Reports2045-23222021-02-0111111610.1038/s41598-021-82346-6B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFFMaha M. Bakhuraysah0Paschalis Theotokis1Jae Young Lee2Amani A. Alrehaili3Pei-Mun Aui4William A. Figgett5Michael F. Azari6John-Paul Abou-Afech7Fabienne Mackay8Christopher Siatskas9Frank Alderuccio10Stephen M. Strittmatter11Nikolaos Grigoriadis12Steven Petratos13Department of Neuroscience, Central Clinical School, Monash UniversityLaboratory of Experimental Neurology and Neuroimmunology, Department of Neurology, AHEPA University HospitalDepartment of Neuroscience, Central Clinical School, Monash UniversityDepartment of Neuroscience, Central Clinical School, Monash UniversityDepartment of Neuroscience, Central Clinical School, Monash UniversityDepartment of Microbiology and Immunology, School of Biomedical Science, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Neuroscience, Central Clinical School, Monash UniversityDepartment of Neuroscience, Central Clinical School, Monash UniversityDepartment of Microbiology and Immunology, School of Biomedical Science, Peter Doherty Institute for Infection and Immunity, University of MelbourneSTEMCELL TechnologiesDepartment of Immunology and Pathology, Central Clinical School, Monash UniversityProgram in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of MedicineLaboratory of Experimental Neurology and Neuroimmunology, Department of Neurology, AHEPA University HospitalDepartment of Neuroscience, Central Clinical School, Monash UniversityAbstract 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.https://doi.org/10.1038/s41598-021-82346-6 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-82346-6 |
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