Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter
Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter
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DOI：
10.1101/443531
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发表时间：
2018-10
期刊：
影响因子：
7.7
通讯作者：
M. Sato-Hashimoto;Tomomi Nozu;Riho Toriba;A. Horikoshi;Miho Akaike;K. Kawamoto;Ayaka Hirose;Yuriko Hayashi;Hiromi Nagai;Wakana Shimizu;Ayaka Saiki;T. Ishikawa;Ruwaida Elhanbly;Takenori Kotani;Yoji Murata;Yasuyuki Saito;M. Naruse;K. Shibasaki;P. Oldenborg;Steffen Jung;T. Matozaki;Y. Fukazawa;H. Ohnishi
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作者：
M. Sato-Hashimoto;Tomomi Nozu;Riho Toriba;A. Horikoshi;Miho Akaike;K. Kawamoto;Ayaka Hirose;Yuriko Hayashi;Hiromi Nagai;Wakana Shimizu;Ayaka Saiki;T. Ishikawa;Ruwaida Elhanbly;Takenori Kotani;Yoji Murata;Yasuyuki Saito;M. Naruse;K. Shibasaki;P. Oldenborg;Steffen Jung;T. Matozaki;Y. Fukazawa;H. Ohnishi
表达CD11c的一个特征性小胶质细胞亚群出现在脑损伤反应中。然而，CD11c+小胶质细胞的功能作用及其诱导机制尚不清楚。在这里，我们报道了信号调节蛋白α (SIRPα)的遗传消融，一种膜蛋白，诱导脑白质中的CD11c+小胶质细胞。缺乏SIRPα生理配体CD47的小鼠和小胶质细胞特异性SIRPα敲除小鼠表现出相同的表型，这表明小胶质细胞SIRPα和CD47在邻近细胞上的相互作用抑制了CD11c+小胶质细胞的出现。SIRPα缺乏不会导致白质可检测到的损伤，但会导致脱髓鞘后修复期特征基因的表达增加。此外，铜酮诱导的脱髓鞘可通过小胶质细胞特异性的SIRPα消融得到缓解。因此，小胶质细胞SIRPα抑制CD11c+小胶质细胞的诱导，而CD11c+小胶质细胞有可能加速受损白质的修复。
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 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 the interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage in the white matter, but resulted in the increased expression of genes 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.