Microglial SIRP alpha regulates the emergence of CD11c(+) microglia and demyelination damage in white matter

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

doi:10.7554/eLife.42025

Microglial SIRP alpha regulates the emergence of CD11c(+) microglia and demyelination damage in white matter

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 JungTakashi Matozaki, Yugo Fukazawa, Hiroshi Ohnishi

Department of Systems Immunology

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

Abstract

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 alpha (SIRP alpha), a membrane protein, induced the emergence of CD11c(+) microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRP alpha, and microglia-specific SIRP alpha-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRP alpha and CD47 on neighbouring cells suppressed the emergence of CD11c(+) microglia. A lack of SIRP alpha 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 SIRP alpha. Thus, microglial SIRP alpha suppresses the induction of CD11c(+) microglia that have the potential to accelerate the repair of damaged white matter.

Original language	English
Article number	42025
Number of pages	29
Journal	eLife
Volume	8
DOIs	https://doi.org/10.7554/eLife.42025
State	Published - 26 Mar 2019

All Science Journal Classification (ASJC) codes

General Neuroscience
General Biochemistry,Genetics and Molecular Biology
General Immunology and Microbiology

Access to Document

10.7554/eLife.42025License: CC BY

Cite this

Sato-Hashimoto, M., Nozu, T., Toriba, R., Horikoshi, A., Akaike, M., Kawamoto, K., Hirose, A., Hayashi, Y., Nagai, H., Shimizu, W., Saiki, A., Ishikawa, T., Elhanbly, R., Kotani, T., Murata, Y., Saito, Y., Naruse, M., Shibasaki, K., Oldenborg, P.-A., ... Ohnishi, H. (2019). Microglial SIRP alpha regulates the emergence of CD11c(+) microglia and demyelination damage in white matter. eLife, 8, Article 42025. https://doi.org/10.7554/eLife.42025

@article{37977a66927d4318812ba42660cb6df1,

title = "Microglial SIRP alpha regulates the emergence of CD11c(+) microglia and demyelination damage in white matter",

abstract = "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 alpha (SIRP alpha), a membrane protein, induced the emergence of CD11c(+) microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRP alpha, and microglia-specific SIRP alpha-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRP alpha and CD47 on neighbouring cells suppressed the emergence of CD11c(+) microglia. A lack of SIRP alpha 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 SIRP alpha. Thus, microglial SIRP alpha suppresses the induction of CD11c(+) microglia that have the potential to accelerate the repair of damaged white matter.",

author = "Miho Sato-Hashimoto and Tomomi Nozu and Riho Toriba and Ayano Horikoshi and Miho Akaike and Kyoko Kawamoto and Ayaka Hirose and Yuriko Hayashi and Hiromi Nagai and Wakana Shimizu and Ayaka Saiki and Tatsuya Ishikawa and Ruwaida Elhanbly and Takenori Kotani and Yoji Murata and Yasuyuki Saito and Masae Naruse and Koji Shibasaki and Per-Arne Oldenborg and Steffen Jung and Takashi Matozaki and Yugo Fukazawa and Hiroshi Ohnishi",

note = "We thank E Urano and T Maegawa for technical assistance. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas ({\textquoteleft}Brain Environment{\textquoteright}), a Grant-in-Aid for Scientific Research (C), and a Grant-in-Aid for Challenging Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a grant from the Takeda Science Foundation of Japan. Funding Ministry of Education, Culture, Sports, Science, and Technology (26111703)",

year = "2019",

month = mar,

day = "26",

doi = "10.7554/eLife.42025",

language = "الإنجليزيّة",

volume = "8",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications Ltd",

}

Sato-Hashimoto, M, Nozu, T, Toriba, R, Horikoshi, A, Akaike, M, Kawamoto, K, Hirose, A, Hayashi, Y, Nagai, H, Shimizu, W, Saiki, A, Ishikawa, T, Elhanbly, R, Kotani, T, Murata, Y, Saito, Y, Naruse, M, Shibasaki, K, Oldenborg, P-A, Jung, S, Matozaki, T, Fukazawa, Y & Ohnishi, H 2019, 'Microglial SIRP alpha regulates the emergence of CD11c(+) microglia and demyelination damage in white matter', eLife, vol. 8, 42025. https://doi.org/10.7554/eLife.42025

TY - JOUR

T1 - Microglial SIRP alpha regulates the emergence of CD11c(+) microglia and demyelination damage in white matter

AU - Sato-Hashimoto, Miho

AU - Nozu, Tomomi

AU - Toriba, Riho

AU - Horikoshi, Ayano

AU - Akaike, Miho

AU - Kawamoto, Kyoko

AU - Hirose, Ayaka

AU - Hayashi, Yuriko

AU - Nagai, Hiromi

AU - Shimizu, Wakana

AU - Saiki, Ayaka

AU - Ishikawa, Tatsuya

AU - Elhanbly, Ruwaida

AU - Kotani, Takenori

AU - Murata, Yoji

AU - Saito, Yasuyuki

AU - Naruse, Masae

AU - Shibasaki, Koji

AU - Oldenborg, Per-Arne

AU - Jung, Steffen

AU - Matozaki, Takashi

AU - Fukazawa, Yugo

AU - Ohnishi, Hiroshi

N1 - We thank E Urano and T Maegawa for technical assistance. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas (‘Brain Environment’), a Grant-in-Aid for Scientific Research (C), and a Grant-in-Aid for Challenging Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a grant from the Takeda Science Foundation of Japan. Funding Ministry of Education, Culture, Sports, Science, and Technology (26111703)

PY - 2019/3/26

Y1 - 2019/3/26

N2 - 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 alpha (SIRP alpha), a membrane protein, induced the emergence of CD11c(+) microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRP alpha, and microglia-specific SIRP alpha-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRP alpha and CD47 on neighbouring cells suppressed the emergence of CD11c(+) microglia. A lack of SIRP alpha 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 SIRP alpha. Thus, microglial SIRP alpha suppresses the induction of CD11c(+) microglia that have the potential to accelerate the repair of damaged white matter.

AB - 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 alpha (SIRP alpha), a membrane protein, induced the emergence of CD11c(+) microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRP alpha, and microglia-specific SIRP alpha-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRP alpha and CD47 on neighbouring cells suppressed the emergence of CD11c(+) microglia. A lack of SIRP alpha 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 SIRP alpha. Thus, microglial SIRP alpha suppresses the induction of CD11c(+) microglia that have the potential to accelerate the repair of damaged white matter.

UR - http://www.scopus.com/inward/record.url?scp=85063712827&partnerID=8YFLogxK

U2 - 10.7554/eLife.42025

DO - 10.7554/eLife.42025

M3 - مقالة

SN - 2050-084X

VL - 8

JO - eLife

JF - eLife

M1 - 42025

ER -

Microglial SIRP alpha regulates the emergence of CD11c(+) microglia and demyelination damage in white matter

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this