Divergent effects of hypoxia on dendritic cell functions
Divergent effects of hypoxia on dendritic cell functions
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DOI：
10.1182/blood-2008-02-142091
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发表时间：
2008-11-01
期刊：
影响因子：
20.3
通讯作者：
Sica, Antonio
中科院分区：
文献类型：
--
作者：
Mancino, Alessandra;Schioppa, Tiziana;Sica, Antonio
树突状细胞（Dendritic cells，DC）是一种专职的抗原呈递细胞（antigen presenting cells，APC），在组织中巡逻以感知危险信号并激活特异性免疫反应。此外，它们还在炎症和组织修复中发挥作用。在这里，我们表明，氧的可用性是必要的，以促进完全单核细胞衍生的DC分化和成熟。低氧张力（缺氧）抑制响应于脂多糖（LPS）的几种分化和成熟标志物（CD 1a、CD 40、CD 80、CD 83、CD 86和MHC II类分子）的表达，以及它们对T细胞功能的刺激能力。这些事件是由趋化因子受体CCR 7的上调受损引起的，CCR 7是成熟DC归巢至淋巴结的必要事件。相反，缺氧强烈上调促炎细胞因子的产生，特别是TNF α和IL-1 β，以及炎性趋化因子受体CCR 5。将缺氧DC皮下注射到小鼠的足垫中导致缺陷DC归巢到引流淋巴结，但增强了注射部位的白细胞募集。因此，缺氧解除了促进炎症和组织修复的DCs中的哨兵功能，我们认为这是一种保护机制，对受损组织的免疫反应。（血。2008; 112：3723-3734）
Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that patrol tissues to sense danger signals and activate specific immune responses. In addition, they also play a role in inflammation and tissue repair. Here, we show that oxygen availability is necessary to promote full monocyte-derived DC differentiation and maturation. Low oxygen tension (hypoxia) inhibits expression of several differentiation and maturation markers (CD1a, CD40, CD80, CD83, CD86, and MHC class II molecules) in response to lipopolysaccharide (LPS), as well as their stimulatory capacity for T-cell functions. These events are paralleled by impaired up-regulation of the chemokine receptor CCR7, an otherwise necessary event for the homing of mature DCs to lymph nodes. In contrast, hypoxia strongly up-regulates production of proinflammatory cytokines, particularly TNF alpha and IL-1 beta, as well as the inflammatory chemokine receptor CCR5. Subcutaneous injection of hypoxic DCs into the footpads of mice results in defective DC homing to draining lymph nodes, but enhanced leukocyte recruitment at the site of injection. Thus, hypoxia uncouples the promotion of inflammatory and tissue repair from sentinel functions in DCs, which we suggest is a safeguard mechanism against immune reactivity to damaged tissues. (Blood. 2008; 112:3723-3734)