SIRPα on CD11c+ cells induces Th17 cell differentiation and subsequent inflammation in the CNS in experimental autoimmune encephalomyelitis.,European Journal of Immunology

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SIRPα on CD11c+ cells induces Th17 cell differentiation and subsequent inflammation in the CNS in experimental autoimmune encephalomyelitis.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-05-21 , DOI: 10.1002/eji.201948410
Taichi Nishimura _{1,

2} , Yasuyuki Saito ₁ , Ken Washio ₁ , Satomi Komori ₁ , Datu Respatika _{1,

3} , Takenori Kotani ₁ , Yoji Murata ₁ , Hiroshi Ohnishi ₄ , Satoshi Mizobuchi ₂ , Takashi Matozaki ₁

Affiliation

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 (Sirpa^ΔDC mice) 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 of Sirpa^ΔDC mice at the onset of EAE. In addition, we found the marked reduction in the number of Th17 cells and DCs in the CNS of Sirpa^ΔDC mice 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.

中文翻译：

CD11c +细胞上的SIRPα在实验性自身免疫性脑脊髓炎中诱导Th17细胞分化以及中枢神经系统随后的炎症。

信号调节蛋白α（SIRPα）主要在2型常规树突状细胞（cDC2s）和巨噬细胞上表达。我们先前显示，系统性缺乏SIRPα的小鼠对实验性自身免疫性脑脊髓炎（EAE）有抵抗力。在这里，我们发现，缺失SIRPα中的CD11c ⁺小鼠（细胞SIRPA ^ΔDC小鼠）也显着改善EAE的发展。cDC上和迁移的DC（mDC的）的频率，以及该Th17细胞，在引流的淋巴结显著降低SIRPA ^ΔDC在EAE发作的小鼠。此外，我们发现在中枢神经系统中的Th17细胞和DC的数量明显减少SIRPA ^ΔDC在EAE高峰期的老鼠。诱导EAE之前可诱导的SIRPα全身性消融阻止了疾病的发展，而EAE发作后的这种系统性消融并未改善疾病的临床症状。我们还发现，在CD11c ⁺ SIRPα配体CD47的细胞特异性消融的小鼠中，EAE的发育被部分减弱。总的来说，我们的结果表明，在CD11c ⁺细胞（例如cDC2s和mDCs）上表达的SIRPα对于EAE的发展是必不可少的，这是引发外周自反应Th17细胞以及中枢神经系统炎症所必需的。

更新日期：2020-05-21

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