Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter
A characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane p...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/42025 |
| _version_ | 1811199517326835712 |
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| author | Miho Sato-Hashimoto Tomomi Nozu Riho Toriba Ayano Horikoshi Miho Akaike Kyoko Kawamoto Ayaka Hirose Yuriko Hayashi Hiromi Nagai Wakana Shimizu Ayaka Saiki Tatsuya Ishikawa Ruwaida Elhanbly Takenori Kotani Yoji Murata Yasuyuki Saito Masae Naruse Koji Shibasaki Per-Arne Oldenborg Steffen Jung Takashi Matozaki Yugo Fukazawa Hiroshi Ohnishi |
| author_facet | Miho Sato-Hashimoto Tomomi Nozu Riho Toriba Ayano Horikoshi Miho Akaike Kyoko Kawamoto Ayaka Hirose Yuriko Hayashi Hiromi Nagai Wakana Shimizu Ayaka Saiki Tatsuya Ishikawa Ruwaida Elhanbly Takenori Kotani Yoji Murata Yasuyuki Saito Masae Naruse Koji Shibasaki Per-Arne Oldenborg Steffen Jung Takashi Matozaki Yugo Fukazawa Hiroshi Ohnishi |
| author_sort | Miho Sato-Hashimoto |
| collection | DOAJ |
| description | A characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane protein, induced the emergence of CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPα, and microglia-specific SIRPα-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage to the white matter, but resulted in the increased expression of genes whose expression is characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter. |
| first_indexed | 2024-04-12T01:49:31Z |
| format | Article |
| id | doaj.art-8bca47c9b3664098b6aa35fd634ec088 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:49:31Z |
| publishDate | 2019-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-8bca47c9b3664098b6aa35fd634ec0882022-12-22T03:52:58ZengeLife Sciences Publications LtdeLife2050-084X2019-03-01810.7554/eLife.42025Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matterMiho Sato-Hashimoto0https://orcid.org/0000-0002-0011-2753Tomomi Nozu1Riho Toriba2Ayano Horikoshi3Miho Akaike4Kyoko Kawamoto5Ayaka Hirose6Yuriko Hayashi7Hiromi Nagai8Wakana Shimizu9Ayaka Saiki10Tatsuya Ishikawa11Ruwaida Elhanbly12Takenori Kotani13Yoji Murata14https://orcid.org/0000-0002-9576-7030Yasuyuki Saito15https://orcid.org/0000-0002-9291-1383Masae Naruse16Koji Shibasaki17https://orcid.org/0000-0003-2330-1749Per-Arne Oldenborg18Steffen Jung19https://orcid.org/0000-0003-4290-5716Takashi Matozaki20https://orcid.org/0000-0002-4393-8416Yugo Fukazawa21Hiroshi Ohnishi22https://orcid.org/0000-0002-2534-5449Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanDepartment of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanDepartment of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanDepartment of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanDepartment of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanDepartment of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanDepartment of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanDepartment of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanDepartment of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanDepartment of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanDepartment of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanDivision of Brain Structure and Function, Faculty of Medical Sciences, University of Fukui, Fukui, Japan; Research Center for Child Mental Development, Faculty of Medical Sciences, University of Fukui, Fukui, Japan; Life Science Innovation Center, University of Fukui, Fukui, JapanDivision of Brain Structure and Function, Faculty of Medical Sciences, University of Fukui, Fukui, Japan; Research Center for Child Mental Development, Faculty of Medical Sciences, University of Fukui, Fukui, Japan; Life Science Innovation Center, University of Fukui, Fukui, Japan; Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, Assiut University, Asyut, EgyptDivision of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, JapanDivision of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, JapanDivision of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, JapanDepartment of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Gunma, JapanDepartment of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Gunma, JapanDepartment of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, Umeå, SwedenDepartment of Immunology, Weizmann Institute of Science, Rehovot, IsraelDivision of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, JapanDivision of Brain Structure and Function, Faculty of Medical Sciences, University of Fukui, Fukui, Japan; Research Center for Child Mental Development, Faculty of Medical Sciences, University of Fukui, Fukui, Japan; Life Science Innovation Center, University of Fukui, Fukui, JapanDepartment of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, JapanA characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane protein, induced the emergence of CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPα, and microglia-specific SIRPα-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage to the white matter, but resulted in the increased expression of genes whose expression is characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.https://elifesciences.org/articles/42025microgliawhite mattertissue repairdemyelinationCD11c |
| spellingShingle | Miho Sato-Hashimoto Tomomi Nozu Riho Toriba Ayano Horikoshi Miho Akaike Kyoko Kawamoto Ayaka Hirose Yuriko Hayashi Hiromi Nagai Wakana Shimizu Ayaka Saiki Tatsuya Ishikawa Ruwaida Elhanbly Takenori Kotani Yoji Murata Yasuyuki Saito Masae Naruse Koji Shibasaki Per-Arne Oldenborg Steffen Jung Takashi Matozaki Yugo Fukazawa Hiroshi Ohnishi Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter eLife microglia white matter tissue repair demyelination CD11c |
| title | Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter |
| title_full | Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter |
| title_fullStr | Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter |
| title_full_unstemmed | Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter |
| title_short | Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter |
| title_sort | microglial sirpα regulates the emergence of cd11c microglia and demyelination damage in white matter |
| topic | microglia white matter tissue repair demyelination CD11c |
| url | https://elifesciences.org/articles/42025 |
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