We recently demonstrated that leukocyte Ig-like receptor 4 (LILRB4) expressed by monocytic acute myeloid leukemia (AML) cells mediates T-cell inhibition and leukemia cell infiltration via its intracellular domain. The cytoplasmic domain of LILRB4 contains three immunoreceptor tyrosine-based inhibitory motifs (ITIMs); the tyrosines at positions 360, 412, and 442 are phosphorylation sites. Here, we analyzed how the ITIMs of LILRB4 in AML cells mediate its function. Our in vitro and in vivo data show that Y412 and Y442, but not Y360, of LILRB4 are required for T-cell inhibition, and all three ITIMs are needed for leukemia cell infiltration. We constructed chimeric proteins containing the extracellular domain of LILRB4 and the intracellular domain of LILRB1 and vice versa. The intracellular domain of LILRB4, but not that of LILRB1, mediates T-cell suppression and AML cell migration. Our studies thus defined the unique signaling roles of LILRB4 ITIMs in AML cells.

中文翻译：

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LILRB4 ITIM介导急性髓样白血病细胞的T细胞抑制和浸润。

我们最近证明单核细胞急性髓性白血病（AML）细胞表达的白细胞Ig样受体4（LILRB4）通过其胞内域介导T细胞抑制和白血病细胞浸润。LILRB4的胞质结构域包含三个基于免疫受体酪氨酸的抑制性基序（ITIM）。在360、412和442位的酪氨酸是磷酸化位点。在这里，我们分析了AML细胞中LILRB4的ITIM如何介导其功能。我们的体外和体内数据显示，LILRB4的Y412和Y442（而不是Y360）是T细胞抑制所必需的，白血病细胞浸润需要全部三个ITIM。我们构建了包含LILRB4的胞外域和LILRB1的胞内域的嵌合蛋白，反之亦然。LILRB4的细胞内结构域，而不是LILRB1的细胞内结构域，介导T细胞抑制和AML细胞迁移。因此，我们的研究确定了LILRB4 ITIM在AML细胞中的独特信号传导作用。