Tolerogenic dendritic cells(DCs)are key players in maintaining immunological homeostasis,dampening immune responses,and promoting tolerance.DC-10,a tolerogenic population of human IL-10-producing DCs characterized by ...Tolerogenic dendritic cells(DCs)are key players in maintaining immunological homeostasis,dampening immune responses,and promoting tolerance.DC-10,a tolerogenic population of human IL-10-producing DCs characterized by the expression of HLA-G and ILT4,play a pivotal role in promoting tolerance via T regulatory type 1(Tr1)cells.Thus far,the absence of markers that uniquely identify DC-10 has limited in vivo studies.By in vitro gene expression profiling of differentiated human DCs,we identified CD141 and CD163 as surface markers for DC-10.The coexpression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of DC-10 from the peripheral blood.CD14+CD16+CD141+CD163+cells isolated from the peripheral blood of healthy subjects(ex vivo DC-10)produced spontaneously and upon activation of IL-10 and limited levels of IL-12.Moreover,in vitro stimulation of allogeneic naive CD4+T cells with ex vivo DC-10 induced the differentiation of alloantigen-specific CD49b+LAG-3+Tr1 cells.Finally,ex vivo DC-10 and in vitro generated DC-10 exhibited a similar transcriptional profile,which are characterized by an anti-inflammatory and pro-tolerogenic signature.These results provide new insights into the phenotype and molecular signature of DC-10 and highlight the tolerogenic properties of circulating DC-10.These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.展开更多
基金This work was supported by research funding from the Italian Telethon Foundation(TGT17G01)the Italian Assodation for Cancer Research,IG-18540,AIRC 2016 to S.G.+1 种基金by COST Action BM1305 A-FAACT(http://www.afactt.eu)and COST Action BM1404 Mye EUNITER(http://www.mye euniter.eu)COST is supported by the EU Framework Program Horizon 2020.MJ.U.was supported by the NSF Graduate Research Fellowship Grant#DGE-1147470.
文摘Tolerogenic dendritic cells(DCs)are key players in maintaining immunological homeostasis,dampening immune responses,and promoting tolerance.DC-10,a tolerogenic population of human IL-10-producing DCs characterized by the expression of HLA-G and ILT4,play a pivotal role in promoting tolerance via T regulatory type 1(Tr1)cells.Thus far,the absence of markers that uniquely identify DC-10 has limited in vivo studies.By in vitro gene expression profiling of differentiated human DCs,we identified CD141 and CD163 as surface markers for DC-10.The coexpression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of DC-10 from the peripheral blood.CD14+CD16+CD141+CD163+cells isolated from the peripheral blood of healthy subjects(ex vivo DC-10)produced spontaneously and upon activation of IL-10 and limited levels of IL-12.Moreover,in vitro stimulation of allogeneic naive CD4+T cells with ex vivo DC-10 induced the differentiation of alloantigen-specific CD49b+LAG-3+Tr1 cells.Finally,ex vivo DC-10 and in vitro generated DC-10 exhibited a similar transcriptional profile,which are characterized by an anti-inflammatory and pro-tolerogenic signature.These results provide new insights into the phenotype and molecular signature of DC-10 and highlight the tolerogenic properties of circulating DC-10.These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.
