Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17
Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17
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DOI：
10.1016/j.immuni.2005.01.011
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发表时间：
2005-03-01
期刊：
影响因子：
32.4
通讯作者：
Ley, K
中科院分区：
文献类型：
--
作者：
Stark, MA;Huo, YQ;Ley, K
中性粒细胞产生的稳态调节被认为与中性粒细胞消除相匹配，以维持血液中大致恒定的数量。在这里，我们表明，IL-17，通过G-CSF调节粒细胞生成的细胞因子，是由γ δ T细胞和非常规α β T细胞。这些嗜中性粒细胞调节性T细胞（Tn）在缺乏白细胞粘附分子的小鼠中扩增，这些小鼠具有嗜中性粒细胞和缺陷性中性粒细胞运输。正常的中性粒细胞迁移到组织，在那里它们变得凋亡并被巨噬细胞和树突细胞吞噬。这抑制了吞噬细胞分泌IL-23，IL-23是一种控制Tn细胞产生IL-17的细胞因子。将野生型中性粒细胞（而非粘附分子缺陷型中性粒细胞）连续转移到β 2整合素缺陷型小鼠体内，可短暂降低嗜中性粒细胞增多症并降低血清IL-17水平。抗体阻断IL-23的p40亚基可减少野生型小鼠中的中性粒细胞数量。这些发现确定了调节体内中性粒细胞产生的主要稳态机制。
Homeostatic regulation of neutrophil production is thought to match neutrophil elimination to maintain approximately constant numbers in the blood. Here, we show that IL-17, a cytokine that regulates granulopoiesis through G-CSF, is made by gamma delta T cells and unconventional alpha beta T cells. These neutrophil-regulatory T cells (Tn) are expanded in mice that lack leukocyte adhesion molecules, which have neutrophilia and defective neutrophil trafficking. Normal neutrophils migrate to tissues, where they become apoptotic and are phagocytosed by macrophages and dendritic cells. This curbs phagocyte secretion of IL-23, a cytokine controlling IL-17 production by Tn cells. Adoptive transfer of wild-type, but not adhesion molecule-deficient, neutrophils into mice deficient in beta(2) integrins transiently decreases neutrophilia and reduces levels of serum IL-17. Antibody blockade of the p40 subunit of IL-23 reduces neutrophil numbers in wild-type mice. These findings identify a major homeostatic mechanism for the regulation of neutrophil production in vivo.