Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice
Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice
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DOI：
10.1016/s1074-7613(00)00035-2
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发表时间：
2000-09-01
期刊：
影响因子：
32.4
通讯作者：
Vivier, E
中科院分区：
文献类型：
--
作者：
Tomasello, E;Desmoulins, PO;Vivier, E
KARAP/DAP12 是一种跨膜多肽，具有基于胞质内免疫受体酪氨酸的激活基序 (ITAM)。 KARAP/DAP12 与造血细胞中的几种激活细胞表面受体相关。在这里，我们报告携带无功能的 KARAP/DAP12 ITAM 的敲入小鼠表现出改变的先天免疫反应。尽管这些小鼠体内存在 NK 细胞，并且其抑制性 MHC I 类受体的功能完整，但 NK 细胞对肿瘤细胞靶标的天然细胞毒性谱系受到限制。 KARAP/DAP12 功能丧失突变小鼠还表现出树突状细胞在皮肤粘膜上皮中的大量积累，这与半抗原特异性接触敏感性受损有关。因此，尽管 KARAP/DAP12 与 CD3 zeta 和 FcR gamma 同源，但它在先天免疫中发挥着特定作用，强调了这些携带 ITAM 的多肽在造血细胞中的非冗余性。
KARAP/DAP12 is a transmembrane polypeptide with an intracytoplasmic immunoreceptor tyrosine-based activation motif (ITAM). KARAP/DAP12 is associated with several activating cell surface receptors in hematopoietic cells. Here, we report that knockin mice bearing a nonfunctional KARAP/DAP12 ITAM present altered innate immune responses. Although in these mice NK cells are present and their repertoire of inhibitory MHC class I receptors is intact, the NK cell spectrum of natural cytotoxicity toward tumor cell targets is restricted. KARAP/DAP12 loss-of-function mutant mice also exhibit a dramatic accumulation of dendritic cells in muco-cutaneous epithelia, associated with an impaired hapten-specific contact sensitivity. Thus, despite its homology with CD3 zeta and FcR gamma, KARAP/DAP12 plays a specific role in innate immunity, emphasizing the nonredundancy of these ITAM-bearing polypeptides in hematopoietic cells.