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Neuroprotection, Neurotoxicity and Neuroinflammation

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

Functional analyses of monocyte-derived plasmacytoid dendritic cells transmigrated across the inflamed blood-brain barrier endothelium

  • P1-340
  • 片山 貴博 / Takahiro Katayama:1 中野 晶子 / Akiko Nakano:1 Igal Ifergan / Ifergan Igal:1 Hania Kebir / Kebir Hania:1 Lecuyer Marc-Andre / Marc-Andre Lecuyer:1 Alvarez Jorge Ivan / Jorge Ivan Alvarez:1 Prat Alexandre / Alexandre Prat:1 
  • 1:CHUM Res Center, Univ of Montreal, Montreal, Canada / CHUM Res Center, Univ of Montreal, Montreal, Canada 

Trafficking of T cells to the CNS and their reactivation by antigen-presenting cells play an essential role in the pathology of multiple sclerosis (MS). We previously reported that CD14+ monocytes can differentiate into CD83+CD209+ myeloid dendritic cells (mDCs) after transmigration across the blood-brain barrier endothelial cells (BBB-ECs) and these mDCs promote the expansion of Th1 and Th17 cells. Here we investigated the function of plasmacytoid DCs (pDCs). Human CD14+ peripheral blood monocytes were co-cultured with TNF-α/IFN-γ-activated BBB-ECs, isolated and phenotyped by FACS. Some of monocytes were shown to be CD83-CD123+, a phenotype compatible with pDCs. The expression of IDO and TGF-β in those monocyte-derived CD123+ pDCs was significant higher than in freshly isolated monocytes. Furthermore, in situ immunostainings of MS CNS samples demonstrated the presence of numerous CD123+IDO+ pDCs in the perivascular spaces of active MS lesions. Human memory CD4+ T cells co-cultured with pDCs showed increased IL-4, decreased INF-γ and enhanced number of CD25+Foxp3+ Tregs compared to when co-cultured with monocytes, suggesting that monocyte-derived pDCs exhibit anti-inflammatory properties. On the other hand, co-culture of anti-CD3 activated CD4+ T cells with pDCs increased the proportion of IFN-γ+ and/or IL-17+ cells in CD25+Foxp3+ cells. Finally, to examine the function of pDCs in experimental autoimmune encephalomyelitis (EAE) mice, PDCA1+B220+ pDCs were collected from the CNS of EAE mice. CD4+ T cells co-cultured with pDCs exhibited anti-inflammatory properties as shown by the lower expression of pro-inflammatory cytokines such as IFN-γ and TNF-α, suggesting that pDCs in the CNS during EAE also exert the anti-inflammatory effects. Our data suggest the possibility that monocytes differentiate into pDCs when migrating across activated BBB-ECs, and that these pDCs induce functional regulation of the CD4 lymphocyte compartment.

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