SIRPα on CD11c+ cells induces Th17 cell differentiation and subsequent inflammation in the CNS in experimental autoimmune encephalomyelitis
SIRPα on CD11c+ cells induces Th17 cell differentiation and subsequent inflammation in the CNS in experimental autoimmune encephalomyelitis
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CD11c+细胞上的SIRPα诱导实验性自身免疫性脑脊髓炎中枢神经系统Th17细胞分化和随后的炎症
DOI：
10.1002/eji.201948410
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发表时间：
2020
影响因子：
5.4
通讯作者：
Matozaki Takashi
中科院分区：
文献类型：
--
作者：
Nishimura Taichi;Saito Yasuyuki;Washio Ken;Komori Satomi;Respatika Datu;Kotani Takenori;Murata Yoji;Ohnishi Hiroshi;Mizobuchi Satoshi;Matozaki Takashi
信号调节蛋白α(Sirpα)主要表达于2型常规树突状细胞(CDC2)和巨噬细胞。我们之前的研究表明，系统缺乏Sirpα的小鼠对实验性自身免疫性脑脊髓炎(EAE)具有抵抗力。在这里，我们发现在小鼠(SirpaαDC小鼠)的CD11c+细胞中缺失SirrpΔ也显著改善了EAE的发展。SirpaΔDC小鼠发病时引流淋巴结中CDC和迁移性DC(MDCs)及Th1 7细胞的频率显著降低。此外，我们还发现，在EAE高峰期，SirpaΔDC小鼠中枢Th1 7细胞和DC数量明显减少。而在EAE诱导前全身可诱导消融Sirpα可阻止疾病的发展，而在EAE发病后不能改善疾病的临床症状。我们还发现，在CD11c+细胞特异性切除Sirpα的配体CD47的小鼠中，EAE的发展被部分减弱。综上所述，我们的结果提示CD11c+细胞，如CDC2和MDCs上表达的sirpα对于EAE的发生是必不可少的，它是启动周围自身反应性Th17细胞和中枢神经系统炎症所必需的。
Signal regulatory protein α (SIRPα) is expressed predominantly on type 2 conventional dendritic cells (cDC2s) and macrophages. We previously showed that mice systemically lacking SIRPα were resistant to experimental autoimmune encephalomyelitis (EAE). Here, we showed that deletion of SIRPα in CD11c+cells of mice (SirpaΔDCmice) also markedly ameliorated the development of EAE. The frequency of cDCs and migratory DCs (mDCs), as well as that of Th17 cells, were significantly reduced in draining lymph nodes ofSirpaΔDCmice at the onset of EAE. In addition, we found the marked reduction in the number of Th17 cells and DCs in the CNS ofSirpaΔDCmice at the peak of EAE. Whereas inducible systemic ablation of SIRPα before the induction of EAE prevented disease development, that after EAE onset did not ameliorate the clinical signs of disease. We also found that EAE development was partially attenuated in mice with CD11c+cell‐specific ablation of CD47, a ligand of SIRPα. Collectively, our results suggest that SIRPα expressed on CD11c+cells, such as cDC2s and mDCs, is indispensable for the development of EAE, being required for the priming of self‐reactive Th17 cells in the periphery as well as for the inflammation in the CNS.
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影响因子：
7.7
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
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
影响因子：
29.7
作者：
Reizis B;Bunin A;Ghosh HS;Lewis KL;Sisirak V
通讯作者：
Sisirak V
影响因子：
4.4
作者：
Tomizawa, Takeshi;Kaneko, Yuka;Matozaki, Takashi
通讯作者：
Matozaki, Takashi
影响因子：
16.8
作者：
Simmons SB;Pierson ER;Lee SY;Goverman JM
通讯作者：
Goverman JM
影响因子：
32.4
作者：
Durai, Vivek;Murphy, Kenneth M.
通讯作者：
Murphy, Kenneth M.