Natural killer dendritic cells are an intermediate of developing dendritic cells
Natural killer dendritic cells are an intermediate of developing dendritic cells
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DOI：
10.1189/jlb.1106674
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发表时间：
2007-06-01
影响因子：
5.5
通讯作者：
Gao, Jian-Xin
中科院分区：
文献类型：
--
作者：
Chen, Li;Calomeni, Edward;Gao, Jian-Xin
NK树突状细胞（DCs; NKDCs）似乎在人类和啮齿动物中作为独特的DC亚群出现，其具有NK细胞和DCs的功能。然而，NKDCs（CD 11 c（+）NK1.1（+））与CD 11 c（+）NK（1.1）DCs的发育关系尚未得到解决。在此，我们发现NKDCs仅存在于稳定状态下的CD 11 c（+）MHC II-细胞区室中，并以组织依赖性方式表达不同水平的DC亚群标志物，如产生IFN的杀伤DC标志物B220。它们可以分化为NK1.1（-）DC，这伴随着在过继转移后MHC II类分子的上调和NK1.1的下调。然而，NK细胞（NK（+）CD 11 c（-））在过继转移后不分化为NK1.1（+）CD 11 c（+）细胞。骨髓来源的Ly 6C（+）单核细胞可能是NKDC的潜在祖细胞，因为其中一些可以在体内分化为CD 11 c（+）NK1.1（+）以及CD 11 c（+）NK1.1（-）细胞。稳态NKDCs具有很强的裂解肿瘤细胞的能力，但呈递抗原的能力很弱。我们的研究表明NKDC是DC发育的中间体。这些细胞似乎具有CD 11 c（+）NK1.1（+）MHC II-的独特表面表型，并具有强的细胞毒性功能，但在稳态下表现出弱的抗原呈递能力。这些发现表明，NKDC可能在连接先天免疫和适应性免疫中发挥关键作用。
NK dendritic cells (DCs; NKDCs) appear to emerge as a distinct DC subset in humans and rodents, which have the functions of NK cells and DCs. However, the developmental relationship of NKDCs (CD11c(+)NK1.1(+)) to CD11c(+)NK(1.1)DCs has not been addressed. Herein, we show that NKDCs exist exclusively in the compartment of CD11c(+)MHC II- cells in the steady state and express variable levels of DC subset markers, such as the IFN-producing killer DC marker B220, in a tissue-dependent manner. They can differentiate into NK1.1(-) DCs, which is accompanied by the up-regulation of MHC Class II molecules and downregulation of NK1.1 upon adoptive transfer. However, NK cells (NK(+)CD11c(-)) did not differentiate into NK1.1(+) CD11c(+) cells upon adoptive transfer. Bone marrow-derived Ly6C(+) monocytes can be a potential progenitor of NKDCs, as some of them can differentiate into CD11c(+)NK1.1(+) as well as CD11c(+)NK1.1(-) cells in vivo. The steady-state NKDCs have a great capacity to lyse tumor cells but little capability to present antigens. Our studies suggest that NKDCs are an intermediate of developing DCs. These cells appear to bear the unique surface phenotype of CD11c(+)NK1.1(+)MHC II- and possess strong cytotoxic function yet show a poor ability to present antigen in the steady state. These findings suggest that NKDCs may play a critical role in linking innate and adaptive immunity.