Impact of β2 integrin deficiency on mouse natural killer cell development and function
Impact of β2 integrin deficiency on mouse natural killer cell development and function
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DOI：
10.1182/blood-2010-10-315457
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发表时间：
2011-03-10
期刊：
影响因子：
20.3
通讯作者：
Ugolini, Sophie
中科院分区：
文献类型：
--
作者：
Crozat, Karine;Eidenschenk, Celine;Ugolini, Sophie
天然杀手（NK）细胞是天生的免疫细胞，它们在人和小鼠中表达白细胞β2整合素家族的成员。这些CD11/CD18异二聚体在白细胞运输，免疫突触形成和共刺激中起关键作用。这些整合素之一CD11b/CD18的细胞表面表达也被认为是小鼠NK细胞成熟的主要标记，但其在NK细胞上的功能已在很大程度上被忽略。使用N-乙基n-硝基库（ENU）诱变，我们在ITGB2基因中产生了一只携带A-> t横向突变的小鼠，从而导致突变，从而阻止了CD18的细胞表面表达及其相关的CD11a，CD11a，CD11b，CD11b，CD11b，和CD11C蛋白。我们表明，β2整联蛋白缺陷型NK细胞在体外具有低反应性表型，并提出了其体内发育程序的改变，其特征在于C-KIT（+）细胞的选择性积累。 NK细胞缺失识别在体内部分改变，而对小鼠巨细胞病毒（MCMV）感染的早期免疫反应正常发生在CD18缺陷小鼠中。因此，最佳NK细胞成熟需要β2整合素，但是这种缺乏症是部分的，可以在MCMV感染期间绕过，突出了抗病毒保护反应的鲁棒性。 （Blood。2011; 117（10）：2874-2882）
Natural killer (NK) cells are innate immune cells that express members of the leukocyte beta 2 integrin family in humans and mice. These CD11/CD18 heterodimers play critical roles in leukocyte trafficking, immune synapse formation, and costimulation. The cell-surface expression of one of these integrins, CD11b/CD18, is also recognized as a major marker of mouse NK-cell maturation, but its function on NK cells has been largely ignored. Using N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated a mouse carrying an A -> T transverse mutation in the Itgb2 gene, resulting in a mutation that prevented the cell-surface expression of CD18 and its associated CD11a, CD11b, and CD11c proteins. We show that beta 2 integrin-deficient NK cells have a hypo-responsive phenotype in vitro, and present an alteration of their in vivo developmental program characterized by a selective accumulation of c-kit(+) cells. NK-cell missing-self recognition was partially altered in vivo, whereas the early immune response to mouse cytomegalovirus (MCMV) infection occurred normally in CD18-deficient mice. Therefore, beta 2 integrins are required for optimal NK-cell maturation, but this deficiency is partial and can be bypassed during MCMV infection, highlighting the robustness of antiviral protective responses. (Blood. 2011; 117(10): 2874-2882)