T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4⁺ T cells.

T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4⁺ T cells.
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T 辅助细胞 1 免疫需要 CD4⁺ T 细胞中补体驱动的 NLRP3 炎性体活性。

DOI:
10.1126/science.aad1210
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发表时间:
2016-06-17
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Kemper C
Kemper C
中科院分区:
其他
文献类型:
--
作者:
Arbore G;West EE;Spolski R;Robertson AAB;Klos A;Rheinheimer C;Dutow P;Woodruff TM;Yu ZX;O'Neill LA;Coll RC;Sher A;Leonard WJ;Köhl J;Monk P;Cooper MA;Arno M;Afzali B;Lachmann HJ;Cope AP;Mayer-Barber KD;Kemper C

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NLRP3炎症小体控制抗原呈递细胞中白细胞介素-1β的成熟,但NLRP3在人类适应性免疫细胞中的直接作用尚未被描述。我们发现NLRP3炎性小体在人CD4+ T细胞中聚集并启动caspase-1依赖性白细胞介素-1β分泌,从而以自分泌方式促进干扰素-γ的产生和T辅助1 (TH1)的分化。NLRP3的组装需要细胞内C5的激活和C5a受体1 (C5aR1)的刺激,而C5aR1受表面表达的C5aR2的负调控。T细胞中异常的NLRP3活性影响人类自身炎症疾病和小鼠炎症和感染模型的炎症反应。我们的研究结果表明,NLRP3炎性体活性并不局限于“先天免疫细胞”,而是正常适应性TH1反应的一个组成部分。
The NLRP3 inflammasome controls interleukin-1β maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described. We found that the NLRP3 inflammasome assembles in human CD4+ T cells and initiates caspase-1–dependent interleukin-1β secretion, thereby promoting interferon-γ production and T helper 1 (TH1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in T cells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to “innate immune cells” but is an integral component of normal adaptive TH1 responses.
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