SIRPα on CD11c + cells induces Th17 cell differentiation and subsequent inflammation in the CNS in experimental autoimmune encephalomyelitis

Autor: Taichi Nishimura, Hiroshi Ohnishi, Satoshi Mizobuchi, Yasuyuki Saito, Datu Respatika, Takenori Kotani, Yoji Murata, Takashi Matozaki, Satomi Komori, Ken Washio
Rok vydání: 2020
Předmět:
Zdroj: European Journal of Immunology. 50:1560-1570
ISSN: 1521-4141
0014-2980
DOI: 10.1002/eji.201948410
Popis: 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 (SirpaΔDC 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 SirpaΔDC 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 SirpaΔDC 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.
Databáze: OpenAIRE
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