Microvesicles released by apoptotic human neutrophils suppress proliferation and IL-2/IL-2 receptor expression of resting T helper cells
Microvesicles released by apoptotic human neutrophils suppress proliferation and IL-2/IL-2 receptor expression of resting T helper cells
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DOI：
10.1002/eji.201546203
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发表时间：
2017-05-01
影响因子：
5.4
通讯作者：
Tykocinski, Lars-Oliver
中科院分区：
文献类型：
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作者：
Shen, Guifen;Krienke, Stefan;Tykocinski, Lars-Oliver
膜包被的微泡（MV）已被确定为细胞间通讯的重要介质。在细胞凋亡过程中，垂死细胞动态释放MV。中性粒细胞是循环中最丰富的白细胞类型。由于它们的寿命非常短，它们很可能是大量凋亡细胞衍生的 MV 的来源。在这里，我们发现凋亡人多形核中性粒细胞（apoPMN-MV）释放的MV，而不是凋亡中性粒细胞本身，以剂量依赖性方式选择性抑制CD25（IL-2Rα）（neg）CD127（IL-7Rα）（pos）Th细胞的增殖。相反，总 T 细胞的增殖不受 MV 的影响。重要的是，apoPMN-MV 抑制 IL-2 的分泌以及 CD25(neg)CD127(pos) Th 细胞的 IL-2 受体 (IL-2R) 的表达和信号传导。添加IL-7强烈降低了MV对T细胞增殖的抑制，而添加IL-2则完全消除了抑制作用。因此，apoPMN-MV 通过下调 IL-2 和 IL-2R 表达和信号传导来抑制 Th 细胞亚群。这可能代表了一种重要机制，可以在缺乏足够的细胞因子刺激的情况下防止静息 T 细胞的激活和扩增，从而维持免疫耐受。
Membrane-coated microvesicles (MVs) have been identified as important mediators in intercellular communication. During the process of apoptosis, dying cells dynamically release MVs. Neutrophils are the most abundant type of leukocytes in the circulation. Due to their very short lifespan, it is likely that they are the source of large amounts of apoptotic cell-derived MVs. Here, we show that MVs released by apoptotic human polymorphonuclear neutrophils (apoPMN-MVs), but not the apoptotic neutrophils themselves, selectively suppress the proliferation of CD25 (IL-2R alpha)(neg) CD127 (IL-7R alpha)(pos) Th cells in a dose-dependent manner. In contrast, the proliferation of total T cells is not affected by MVs. Importantly, apoPMN-MVs suppress the secretion of IL-2 as well as the expression of and signaling via the IL-2 receptor (IL-2R) by CD25(neg)CD127(pos) Th cells. Addition of IL-7 strongly reduced the suppression of T-cell proliferation by MVs and the addition of IL-2 completely abrogated the suppressive effect. Thus, apoPMN-MVs suppressed a subset of Th cells by downregulating IL-2 and IL-2R expression and signaling. This may represent an important mechanism to prevent the activation and expansion of resting T cells in the absence of sufficient cytokine stimulation, and thereby maintaining immune tolerance.