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

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�DC 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�DC
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�DC 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.
Keywords: Autoimmunity � CD47 � Dendritic Cells � EAE � SIRPα