CD160 is essential for NK-mediated IFN-γ production.
CD160 is essential for NK-mediated IFN-γ production.
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DOI：
10.1084/jem.20131601
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发表时间：
2015-03-09
期刊：
影响因子：
--
通讯作者：
Fu YX
中科院分区：
文献类型：
--
作者：
Tu TC;Brown NK;Kim TJ;Wroblewska J;Yang X;Guo X;Lee SH;Kumar V;Lee KM;Fu YX
屠呦呦等人。产生了一种新的CD160缺陷小鼠，并显示出NK细胞介导的肿瘤清除和干扰素-γ产生受损。CD160+NK细胞分泌干扰素-γ的功能与CD160+−NK细胞不同。NK来源的细胞因子对自然杀伤细胞(NK)的功能起着重要作用，但对这些细胞因子是如何调节的却知之甚少。CD160在人类活化的NK或T细胞上表达，但其功能尚不清楚。我们建立了CD160缺陷小鼠来检测其功能。虽然CD160−/−小鼠在淋巴细胞发育方面没有异常，但CD160−/−小鼠对NK敏感肿瘤的控制严重受损。令人惊讶的是，NK细胞的细胞毒作用没有受到损害，但NK细胞分泌的干扰素-γ(干扰素-γ)显著减少。功能靶向CD160信号的可溶性CD160-Ig也损害了肿瘤控制和干扰素-γ的产生，提示CD160信号的积极作用。利用双向骨髓移植和细胞培养，我们已经确定了CD160在NK细胞上的内在作用，以及它在非NK细胞上的受体，以调节细胞因子的产生。为了证明CD160+NK细胞亚群在控制依赖NK的肿瘤生长方面的充分性，瘤内转移CD160+NK组分导致了CD160−/−荷瘤小鼠肿瘤的消退，这表明CD160+NK细胞亚群对控制早期肿瘤具有明显的治疗潜力。因此，CD160不仅是一个重要的生物标志物，而且在功能上控制着NK细胞的细胞因子的产生。
Tu et al. generated a novel CD160-deficient mouse and showed impaired NK cell–mediated tumor elimination and IFN-γ production. CD160+ NK cells are functionally distinct in secretion of IFN-γ from their CD160− NK cell counterparts. NK-derived cytokines play important roles for natural killer (NK) function, but how the cytokines are regulated is poorly understood. CD160 is expressed on activated NK or T cells in humans but its function is unknown. We generated CD160-deficient mice to probe its function. Although CD160−/− mice showed no abnormalities in lymphocyte development, the control of NK-sensitive tumors was severely compromised in CD160−/− mice. Surprisingly, the cytotoxicity of NK cells was not impaired, but interferon-γ (IFN-γ) secretion by NK cells was markedly reduced in CD160−/− mice. Functionally targeting CD160 signaling with a soluble CD160-Ig also impaired tumor control and IFN-γ production, suggesting an active role of CD160 signaling. Using reciprocal bone marrow transfer and cell culture, we have identified the intrinsic role of CD160 on NK cells, as well as its receptor on non-NK cells, for regulating cytokine production. To demonstrate sufficiency of the CD160+ NK cell subset in controlling NK-dependent tumor growth, intratumoral transfer of the CD160+ NK fraction led to tumor regression in CD160−/− tumor-bearing mice, indicating demonstrable therapeutic potential for controlling early tumors. Therefore, CD160 is not only an important biomarker but also functionally controls cytokine production by NK cells.
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影响因子：
6.4
作者：
Kakuta, S;Tagawa, Y;Iwakura, Y
通讯作者：
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DOI：
10.1073/pnas.0902115106
发表时间：
2009-04-14
影响因子：
11.1
作者：
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通讯作者：
Ware, Carl F.
影响因子：
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作者：
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