Trapping of misdirected dendritic cells in the granulomatous lesions of giant cell arteritis
Trapping of misdirected dendritic cells in the granulomatous lesions of giant cell arteritis
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DOI：
10.1016/s0002-9440(10)64458-6
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发表时间：
2002-11-01
影响因子：
6
通讯作者：
Weyand, CM
中科院分区：
文献类型：
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作者：
Krupa, WM;Dewan, M;Weyand, CM
未成熟的树突细胞（DC）散布在整个外周组织中，并作为对抗原环境取样的哨兵。活化后，它们改变其趋化因子受体谱并向淋巴组织迁移。在到达时，它们已经成熟为表达共刺激分子的产生趋化因子的DC，并且可以引发幼稚T细胞。正常颞动脉含有未成熟的树突状细胞，位于中膜-外膜边缘。在受巨细胞动脉炎影响的颞动脉中，DC高度富集和活化，并且已经成熟为产生趋化因子CCL 18、CCL 19和CCL 21的完全分化的细胞。与它们的成熟度相一致，肉芽肿病变中的DC具有趋化因子受体CCR 7。CCR 7结合CCL 19和CCL 21，导致高度活化的DC被捕获在外周组织部位。共刺激分子CD 86是DC/T细胞相互作用的关键分子，由动脉壁中捕获的DC亚群表达。DC/T细胞相互作用不涉及白细胞介素-12;白细胞介素-12 p40的转录物在血管炎性浸润中不存在。我们认为，分化的树突状细胞和自分泌和旁分泌作用的趋化因子在gramilomatous病变误导树突状细胞远离他们通常的旅程淋巴器官，并在维持T细胞活化和肉芽肿形成巨细胞动脉炎的关键。
immature dendritic cells (DCs) are scattered throughout peripheral tissues and act as sentinels that sample the antigenic environment. After activation, they modify their chemokine receptor profile and migrate toward lymphoid tissues. On arrival, they have matured into chemokine-producing DCs that express costimulatory molecules and can prime naive T cells. Normal temporal arteries contain immature DCs that are located at the media-adventitia border. in temporal arteries affected by giant cell arteritis, DCs are highly enriched and activated and have matured into fully differentiated cells producing the chemokines, CCL18, CCL19, and CCL21. In keeping with their advanced maturation, DCs in the granulomatous lesions possess the chemokine receptor, CCR7. CCR7 binds CCL19 and CCL21, causing the highly activated DCs to be trapped in the peripheral tissue site. The co-stimulatory molecule, CD86, which is critical for DC/T-celI interaction, is expressed by a subset of DCs captured in the arterial wall. DC/T-cell interaction does not involve interleukin-12; transcripts for interleukin-12 p40 are absent in the vasculitic infiltrates. We propose that differentiation of DCs and the autocrine and paracrine actions of chemokines in gramilomatous lesions misdirect DCs away from their usual journey to lymphoid organs and are critical in maintaining T-cell activation and granuloma formation in giant cell arteritis.