Inhibitory NK receptor Ly49Q is expressed on subsets of dendritic cells in a cellular maturation- and cytokine stimulation-dependent manner
Inhibitory NK receptor Ly49Q is expressed on subsets of dendritic cells in a cellular maturation- and cytokine stimulation-dependent manner
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DOI：
10.4049/jimmunol.174.8.4621
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Karasuyama, H
中科院分区：
文献类型：
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作者：
Toyama-Sorimachi, N;Omatsu, Y;Karasuyama, H
Ly49Q 是 Ly49 家族的成员，在 Gr-1(+) 细胞上表达，但在 NK 和 NKT 细胞上不表达。 Ly49Q 似乎通过 ITIM 介导的信号传导参与调节细胞骨架结构。我们提供的证据表明，某些成熟状态的树突状细胞 (I)Cs) 表达 Ly49Q，并且 IFN-α 在其调节中发挥重要作用。新鲜制备的小鼠浆细胞样前 DC 以及 Flt3L 诱导的浆细胞样前 DC 表达 Ly49Q，而新鲜制备的骨髓 DC 则不表达。然而，GM-CSF 诱导的骨髓 DC 表现出低水平的 Ly49Q 表达，而 IFN-a 显着增强了这种表达。相比之下，其他细胞因子和 TLR 配体（例如 TNF-α、IL-6、LPS 和 CpG-ODN）对 Ly49Q 表达影响很小或没有影响。所有检查的小鼠品系中的浆细胞样前 I)C 均表达 Ly49Q。在 129、NZB 和 NZW 三种限制性小鼠品系中观察到 Ly49Q 在髓样 DC 上的组成型表达。从其他 Ly49 家族成员中可以看出，Ly49Q 表达受到 MHC 1 类表达的影响。同时，Ly49Q具有多态性，包括至少三个等位基因。多态性残基位于茎和碳水化合物识别结构域内，其中两个位于碳水化合物识别结构域的环3和环6中，位于涉及Ly49A与H-2D(d)相互作用的区域中。因此，根据 IFN-α，我们的结果表明 Ly49Q 通过识别 MHC I 类或相关分子，在某些 DC 亚群的生物学功能中发挥作用。
Ly49Q is a member of the Ly49 family that is expressed on Gr-1(+) cells but not on NK and NKT cells. Ly49Q appears to be involved in regulating cytoskeletal architectures through ITIM-mediated signaling. We provide evidence that dendritic cells (I)Cs) of certain maturational states expressed Ly49Q, and that IFN-alpha plays an important role in its regulation. Freshly prepared murine plasmacytoid pre-DCs as well as Flt3L-induced plasmacytoid pre-DCs expressed Ly49Q, whereas freshly prepared myeloid DCs did not. However, GM-CSF-induced myeloid DCs showed low levels of Ly49Q expression, and this was significantly enhanced by IFN-a. In contrast, other cytokines and ligands for TLRs such as TNF-alpha, IL-6, LPS, and CpG-ODN had little or no effect on Ly49Q expression. Plasmacytoid pre-I)Cs in all mouse strains examined expressed Ly49Q. Constitutive expression of Ly49Q on myeloid DCs was observed in three restricted mouse strains including 129, NZB, and NZW. As can be seen in other Ly49 family members, Ly49Q expression was affected by MHC class 1 expression. At the same time, Ly49Q possessed polymorphisms, including at least three alleles. The polymorphic residues lay within the stalk and carbohydrate recognition domain, and two of them, in loop 3 and loop 6 of the carbohydrate recognition domain, are located in the region implicated in the interaction of Ly49A with H-2D(d). Therefore, depending on IFN-alpha our results imply that Ly49Q serves a role for the biological functions of certain DC subsets through recognition of MHC class I or related molecules.