IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium.
IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium.
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DOI：
10.4049/jimmunol.1600138
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发表时间：
2016-09-15
期刊：
影响因子：
--
通讯作者：
Pober JS
中科院分区：
文献类型：
--
作者：
Liu R;Lauridsen HM;Amezquita RA;Pierce RW;Jane-Wit D;Fang C;Pellowe AS;Kirkiles-Smith NC;Gonzalez AL;Pober JS
急性炎症的一个典型特征是中性粒细胞的组织渗透，这是一个多步骤的过程，涉及循环中的白细胞与白介素1或肿瘤坏死因子α激活的微血管内皮细胞和周细胞的细胞间顺序相互作用，形成毛细血管后小静脉的壁。最初的浸润性细胞聚集在靠近PC的血管周围。IL-17是一种促炎细胞因子，通过IL-17RA和IL-17RC亚基形成的异二聚体受体作用于靶细胞，也促进中性粒细胞炎症，但其对血管细胞的作用尚不清楚。我们报道，培养的人内皮细胞和PC都强烈表达IL-17RC，虽然两种细胞都不表达太多IL-17RA，但PC的表达明显高于ECs。IL-17单独或与肿瘤坏死因子协同作用可显著改变培养的人PC的炎症基因表达，但不能改变内皮细胞的表达。RNA-seq分析确定了许多IL-17诱导的PC转录本，编码已知的刺激中性粒细胞介导的免疫的蛋白质。IL-17激活的PC的条件培养液(CM)诱导百日咳毒素敏感的中性粒细胞极化，可能是由PC分泌的趋化因子介导的，并刺激中性粒细胞产生促炎分子，包括肿瘤坏死因子、IL-1α、IL-1β和IL-8。此外，IL-17激活的PC而不是ECs可以通过产生G-CSF和GM-CSF来延长中性粒细胞的存活，延迟线粒体外膜的通透性和caspase 9的激活。重要的是，经IL-17处理的PC经CM激活后，中性粒细胞的吞噬能力增强。我们得出结论，IL-17在微血管壁内的主要靶点是PC，而不是ECs，IL-17激活的PC可以调节血管周围组织空间内的中性粒细胞功能。
A classical hallmark of acute inflammation is neutrophil infiltration of tissues, a multi-step process that involves sequential cell-cell interactions of circulating leukocytes with interleukin (IL)-1- or tumor necrosis factor-α (TNF)-activated microvascular endothelial cells (ECs) and pericytes (PCs) that form the wall of the postcapillary venules. The initial infiltrating cells accumulate perivascularly in close proximity to PCs. IL-17, a pro-inflammatory cytokine that acts on target cells via a heterodimeric receptor formed by IL-17RA and IL-17RC subunits, also promotes neutrophilic inflammation but its effects on vascular cells are less clear. We report that both cultured human ECs and PCs strongly express IL-17RC and, while neither cell type expresses much IL-17RA, PCs express significantly more than ECs. IL-17, alone or synergistically with TNF, significantly alters inflammatory gene expression in cultured human PCs but not ECs. RNA-seq analysis identifies many IL-17-induced transcripts in PCs encoding proteins known to stimulate neutrophil-mediated immunity. Conditioned media (CM) from IL-17-activated PCs, but not ECs, induce pertussis toxin-sensitive neutrophil polarization, likely mediated by PC-secreted chemokines, and also stimulate neutrophil production of pro-inflammatory molecules, including TNF, IL-1α, IL-1β, and IL-8. Furthermore, IL-17-activated PCs but not ECs can prolong neutrophil survival by producing G-CSF and GM-CSF, delaying the mitochondria outer membrane permeabilization and caspase 9 activation. Importantly, neutrophils exhibit enhanced phagocytic capacity after activation by CM from IL-17-treated PCs. We conclude that PCs, not ECs, are the major target of IL-17 within the microvessel wall and that IL-17-activated PCs can modulate neutrophil functions within the perivascular tissue space.
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影响因子：
4.5
作者：
Bosteen, Markus H.;Tritsaris, Katerina;Hansen, Anker J.;Dissing, Steen
通讯作者：
Dissing, Steen
影响因子：
20.3
作者：
Tehranchi, R;Fadeel, B;Hellstrom-Lindberg, E
通讯作者：
Hellstrom-Lindberg, E
影响因子：
4.8
作者：
Lauridsen, Holly M.;Pober, Jordan S.;Gonzalez, Anjelica L.
通讯作者：
Gonzalez, Anjelica L.
DOI：
10.1161/atvbaha.110.217117
发表时间：
2011-01-01
影响因子：
8.7
作者：
Maier, Cheryl L.;Pober, Jordan S.
通讯作者：
Pober, Jordan S.
影响因子：
30.5
作者：
Stark, Konstantin;Eckart, Annekathrin;Massberg, Steffen
通讯作者：
Massberg, Steffen