Immunoglobulin directly enhances differentiation of oligodendrocyte-precursor cells and remyelination
Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease characterized by multiple lesions in the central nervous system. Although the role of B cells in MS pathogenesis has attracted much attention, but the detailed mechanisms remain unclear. To investigate the effects of B cells o...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-36532-3 |
| _version_ | 1797453220131373056 |
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| author | Yaguang Li Daisuke Noto Yasunobu Hoshino Miho Mizuno Soichiro Yoshikawa Sachiko Miyake |
| author_facet | Yaguang Li Daisuke Noto Yasunobu Hoshino Miho Mizuno Soichiro Yoshikawa Sachiko Miyake |
| author_sort | Yaguang Li |
| collection | DOAJ |
| description | Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease characterized by multiple lesions in the central nervous system. Although the role of B cells in MS pathogenesis has attracted much attention, but the detailed mechanisms remain unclear. To investigate the effects of B cells on demyelination, we analyzed a cuprizone-induced demyelination model, and found that demyelination was significantly exacerbated in B cell-deficient mice. We next investigated whether immunoglobulin affected the myelin formation process using organotypic brain slice cultures and revealed that remyelination was improved in immunoglobulin-treated groups compared with the control group. Analysis of oligodendrocyte-precursor cell (OPC) monocultures showed that immunoglobulins directly affected on OPCs and promoted their differentiation and myelination. Furthermore, OPCs expressed FcγRI and FcγRIII, two receptors that were revealed to mediate the effects of IgG. To the best of our knowledge, this is the first study to demonstrate that B cells act in an inhibitory manner against cuprizone-induced demyelination, while immunoglobulins enhance remyelination following demyelination. Analysis of the culture system revealed that immunoglobulins directly act on OPCs to promote their differentiation and myelination. Future studies to elucidate the effects of immunoglobulins on OPCs in vivo and the detailed mechanisms of these effects may lead to new treatments for demyelinating diseases. |
| first_indexed | 2024-03-09T15:19:38Z |
| format | Article |
| id | doaj.art-84a02c7f508e48d196e4436ddc7cc28d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:19:38Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-84a02c7f508e48d196e4436ddc7cc28d2023-11-26T12:52:14ZengNature PortfolioScientific Reports2045-23222023-06-0113111010.1038/s41598-023-36532-3Immunoglobulin directly enhances differentiation of oligodendrocyte-precursor cells and remyelinationYaguang Li0Daisuke Noto1Yasunobu Hoshino2Miho Mizuno3Soichiro Yoshikawa4Sachiko Miyake5Department of Immunology, Juntendo University School of MedicineDepartment of Immunology, Juntendo University School of MedicineDepartment of Neurology, Juntendo University School of MedicineDepartment of Immunology, Juntendo University School of MedicineDepartment of Immunology, Juntendo University School of MedicineDepartment of Immunology, Juntendo University School of MedicineAbstract Multiple sclerosis (MS) is an inflammatory demyelinating disease characterized by multiple lesions in the central nervous system. Although the role of B cells in MS pathogenesis has attracted much attention, but the detailed mechanisms remain unclear. To investigate the effects of B cells on demyelination, we analyzed a cuprizone-induced demyelination model, and found that demyelination was significantly exacerbated in B cell-deficient mice. We next investigated whether immunoglobulin affected the myelin formation process using organotypic brain slice cultures and revealed that remyelination was improved in immunoglobulin-treated groups compared with the control group. Analysis of oligodendrocyte-precursor cell (OPC) monocultures showed that immunoglobulins directly affected on OPCs and promoted their differentiation and myelination. Furthermore, OPCs expressed FcγRI and FcγRIII, two receptors that were revealed to mediate the effects of IgG. To the best of our knowledge, this is the first study to demonstrate that B cells act in an inhibitory manner against cuprizone-induced demyelination, while immunoglobulins enhance remyelination following demyelination. Analysis of the culture system revealed that immunoglobulins directly act on OPCs to promote their differentiation and myelination. Future studies to elucidate the effects of immunoglobulins on OPCs in vivo and the detailed mechanisms of these effects may lead to new treatments for demyelinating diseases.https://doi.org/10.1038/s41598-023-36532-3 |
| spellingShingle | Yaguang Li Daisuke Noto Yasunobu Hoshino Miho Mizuno Soichiro Yoshikawa Sachiko Miyake Immunoglobulin directly enhances differentiation of oligodendrocyte-precursor cells and remyelination Scientific Reports |
| title | Immunoglobulin directly enhances differentiation of oligodendrocyte-precursor cells and remyelination |
| title_full | Immunoglobulin directly enhances differentiation of oligodendrocyte-precursor cells and remyelination |
| title_fullStr | Immunoglobulin directly enhances differentiation of oligodendrocyte-precursor cells and remyelination |
| title_full_unstemmed | Immunoglobulin directly enhances differentiation of oligodendrocyte-precursor cells and remyelination |
| title_short | Immunoglobulin directly enhances differentiation of oligodendrocyte-precursor cells and remyelination |
| title_sort | immunoglobulin directly enhances differentiation of oligodendrocyte precursor cells and remyelination |
| url | https://doi.org/10.1038/s41598-023-36532-3 |
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