Dendritic Cell-Derived IL-32α: A Novel Inhibitory Cytokine of NK Cell Function
Dendritic Cell-Derived IL-32α: A Novel Inhibitory Cytokine of NK Cell Function
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DOI：
10.4049/jimmunol.1601477
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发表时间：
2017-08-15
影响因子：
4.4
通讯作者：
Klechevsky, Eynav
中科院分区：
文献类型：
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作者：
Gorvel, Laurent;Korenfeld, Daniel;Klechevsky, Eynav
树突状细胞（DCs）产生的细胞因子在很大程度上决定了免疫的方向。转录分析表明，除了IL-15，IL-32是唯一的其他细胞因子表达的人朗格汉斯细胞。IL-32是以四种主要同种型存在的人细胞因子。目前，对各种IL-32亚型的调节和功能知之甚少。在这项研究中，我们发现IL-15是DC中IL-32 α的有效诱导剂。由于IL-15促进NK细胞活化，我们研究了IL-32和IL-15之间的相互作用及其在NK细胞活性中的作用。我们发现，IL-32 α作用于NK细胞，抑制IL-15介导的STAT 5磷酸化，并抑制其IL-15诱导的效应分子表达和细胞溶解能力。IL-32 α还通过下调IL-15诱导的IL-18产生而作用于DC，IL-18是NK细胞活性中的重要细胞因子。在DC：NK细胞共培养期间阻断IL-32 α增强NK细胞效应分子表达以及它们的细胞溶解能力。总之，我们的研究结果表明IL-32 α对IL-15介导的NK细胞活性具有反馈抑制作用。
Cytokines produced by dendritic cells (DCs) can largely determine the direction of immunity. Transcriptional analysis revealed that besides IL-15, IL-32 was the only other cytokine expressed by human Langerhans cells. IL-32 is a human cytokine that exists in four main isoforms. Currently, little is known about the regulation and function of the various IL-32 isoforms. In this study, we found that IL-15 is a potent inducer of IL-32 alpha in DCs. Because IL-15 promotes NK cell activation, we investigated the interplay between IL-32 and IL-15 and their role in NK cell activity. We show that IL-32 alpha acts on NK cells to inhibit IL-15-mediated STAT5 phosphorylation and to suppress their IL-15-induced effector molecule expression and cytolytic capacity. IL-32 alpha also acted on DCs by downregulating IL-15-induced IL-18 production, an important cytokine in NK cell activity. Blocking IL-32 alpha during DC: NK cell coculture enhanced NK cell effector molecule expression as well as their cytolytic capacity. Taken together, our findings suggest a feedback inhibition of IL-15-mediated NK cell activity by IL-32 alpha.