Development of murine plasmacytoid dendritic cells defined by increased expression of an inhibitory NK receptor, Ly49Q

Development of murine plasmacytoid dendritic cells defined by increased expression of an inhibitory NK receptor, Ly49Q
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DOI:
10.4049/jimmunol.174.11.6657
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发表时间:
2005-06-01
影响因子:
4.4
通讯作者:
Inaba, K
Inaba, K
中科院分区:
医学2区
文献类型:
--
作者:
Omatsu, Y;Iyoda, T;Inaba, K

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浆细胞样树突状细胞(PDCs)在小鼠中通过独特的标志物组合来定义:CD 11 c,B220和Ly 6C/G。我们以前曾报道过PDCs表达Ly 49 Q,一种凝集素型杀伤细胞抑制受体。我们现在发现Ly 49 Q的不同表达水平定义了骨髓中PDCs的连续发育阶段。尽管脾脏和淋巴结中的PDC表达高水平的Ly 49 Q,但骨髓中相当一部分CD 11 c(+)B220(+)PDC缺乏Ly 49 Q,以及CD 4和MHC H。纯化的Ly 49 Q(-)骨髓PDCs在过夜培养后自发上调Ly 49 Q,而无细胞增殖,并获得典型的脾脏PDCs的大多数特征。当暴露于TLR配体,如日本的CpG-寡脱氧核苷酸和血凝病毒(仙台病毒)时,Ly 49 Q-PDC增加CD 86和MHC H类表达,但产生比Ly 49 Q(+)PDC少的IFN-α β、IL-6和IL-12 p70,尽管它们能够产生相当量的TNF-α。然而,有趣的是,Ly 49 Q-PDC不响应于TLR 2配体Pam 3SCK产生TNF-α(4),而Ly 49 Q(+)PDC产生TNF-α。因此,Ly 49 Q是鉴定参与先天免疫的PDCs前体形式的新标记物。
Plasmacytoid dendritic cells (PDCs) are defined in mice by a unique combination of markers: CD11c, B220, and Ly6C/G. We have reported previously that PDCs express Ly49Q, a lectin-type killer cell inhibitory receptor. We now find that different expression levels of Ly49Q define sequential developmental stages of PDCs in bone marrow. Although PDCs in spleen and lymph nodes express high levels of Ly49Q, a significant portion of CD11c(+)B220(+) PDCs in bone marrow lack Ly49Q, as well as the CD4 and MHC H. Purified Ly49Q(-) marrow PDCs spontaneously up-regulate Ly49Q after overnight culture without cell proliferation and acquire most features of typical PDCs in spleen. When exposed to TLR ligands, such as CpG-oligodeoxynucleotide and hemagglutinating virus of Japan (Sendai virus), Ly49Q- PDCs increase CD86 and MHC class H expression but produce less IFN-alpha beta, IL-6, and IL-12p70 than Ly49Q(+) PDCs, although they are able to produce comparable amounts of TNF-alpha. However, interestingly, Ly49Q- PDCs do not produce TNF-a in response to the TLR2 ligand, Pam3SCK(4), whereas Ly49Q(+) PDCs did. Therefore, Ly49Q is a new marker to identify a precursor form of PDCs that participates in innate immunity.