Giant cell arteritis: dendritic cells take two T's to tango.
Giant cell arteritis: dendritic cells take two T's to tango.
复制标题
巨细胞动脉炎：树突状细胞需要两个T才能跳探戈。
DOI：
10.1161/circresaha.109.194266
复制
发表时间：
2009
影响因子：
20.1
通讯作者：
Arditi,Moshe
中科院分区：
文献类型：
--
作者：
Yilmaz,Atilla;Arditi,Moshe
动脉中的慢性炎症有多种形式，原因也有很大不同。动脉炎症最常见的形式是动脉粥样硬化，其中炎症通常限于新生内膜，有时限于中等和较大动脉的中层。然而，动脉的深层也会发炎。巨细胞动脉炎（GCA）是慢性炎症的一个例子，通常会影响动脉壁的所有层，包括外膜。GCA的快速发展的同心性增生性血管病变通常发生在主动脉的大分支，特别是颈动脉和颞动脉。1 GCA的临床特征通常是由管腔阻塞引起的下游组织缺血的结果，可能相当温和（例如头痛），但可能包括失明、颌跛行、动脉瘤、动脉破裂、中风和死亡。1诊断可通过活检证实，病变组织表现为肉芽肿性全动脉炎和巨细胞（因此得名）。1 GCA中的炎性病变由活化的T细胞、树突状细胞（DCs）和巨噬细胞组成。[2] GCA的病因尚不清楚，但与其他形式的动脉炎症一样，GCA似乎涉及耐受性的破坏，这似乎是由宿主防御和动脉壁之间的某种相互作用引起的。因此，GCA反映了自身免疫现象的特征，以及原发性免疫缺陷，但两者的细节尚不清楚。最近，在了解GCA的发病机制方面取得了重大进展，涉及获得性免疫，特别是DC，作为一个组成部分。DC是特化的抗原呈递细胞，其在针对病原体的每种免疫应答中作为有效的T细胞活化剂被需要。4 DC配备有模式识别受体，特别是Toll样受体（TLR），其识别微生物基序，诱导DC成熟，并随后获得激活T细胞对抗病原体的能力。4在正常的未发炎动脉中，未成熟和静息的髓样DC位于外膜-中膜边界周围的环状结构中，这表明DC是形成血管壁中第一线免疫防御的一部分的哨兵。2在生物工程化的人大血管中，壁嵌入的DC而不是单核细胞或巨噬细胞可以触发壁内适应性免疫应答。5在GCA过程中，受影响动脉外膜中血管髓样DC的数量显著增加。5髓样DC的活化被认为是GCA发病机制中的第一个关键步骤。2虽然这些髓样DC激活的原因尚不清楚，但一些研究者认为肺炎衣原体感染可能是一个促成因素。6血管DC在GCA免疫反应中的重要作用先前在颞动脉-SCID小鼠嵌合体中得到了证实。而用脂多糖刺激血管髓样DC（通过TLR-4）导致外膜中活化的CD 4 + T细胞的显著募集，7使用抗CD 83抗体特异性抑制髓样DC完全消除GCA中的血管炎症。3最近，Pryshchep等人描述了TLR 1至9在髓样和浆细胞样DC上的不同表达模式，其依赖于动脉的解剖定位。值得注意的是，每个血管区域的独特TLR谱表明免疫传感功能的专业化。7这一事实提出了一个问题，即通过不同的TLR激活DC是否会导致相似或不同的血管免疫反应。
Chronic inflammation in arteries takes many forms and the causes vary markedly. The most common form of arterial inflammation is atherosclerosis, where inflammation is generally limited to the neointima and sometimes the medial layer of medium and larger arteries. However, the deeper layers of arteries can also become inflamed as well. Giant cell arteritis (GCA) constitutes an example of chronic inflammation that may often affect all layers of the arterial wall, including the adventitia. 1 The rapidly evolving concentric hyperplastic vascular lesions of GCA typically occur in large branches of the aorta, particularly the carotid and temporal arteries. 1 Clinical features of GCA are generally the result of the downstream tissue ischemia caused by luminal obstruction and may be rather modest (eg, headaches) but can include blindness, jaw claudication, aneurysm, arterial rupture, stroke, and death. 1 The diagnosis can be confirmed by biopsy, and diseased tissues exhibit a granulomatous panarteritis and the presence of giant cells (hence, the name). 1 Inflammatory lesions in GCA consist of activated T cells, dendritic cells (DCs), and macrophages. 2 The causes of GCA are not well understood, but as is the case with other forms of arterial inflammation, GCA appears to involve a breakdown of tolerance that seems to result from some interaction between host defenses and the arterial wall. 3 Hence, GCA reflects features of autoimmune phenomena, as well as primary immune defects, but the details of both are unclear. Recently, major advances have been made in understanding the pathogenesis of GCA, implicating adaptive immunity, particularly DCs, as an integral part. DCs are specialized antigen-presenting cells, which are required as potent T-cell activators in each immune response against pathogens. 4 DCs are equipped with pattern recognition receptors, particularly Toll-like receptors (TLRs), which recognize microbial motifs, induce DC maturation, and subsequently acquire the ability to activate T cells against the pathogen. 4 In normal uninflamed arteries, immature and resting myeloid DCs are located in a ring-like structure around the adventitia–media border, which suggests that DCs are sentinels that form part of the first-line immune defense in the vessel wall. 2 In bioengineered human macrovessels, wall-embedded DCs but not monocytes or macrophages can trigger an intramural adaptive immune response. 5 During GCA, the number of vascular myeloid DCs significantly increases in the adventitia of affected arteries. 5 The activation of myeloid DCs is believed to be the first critical step in the pathogenesis of GCA. 2 Although the reasons for the activation of these myeloid DCs are unknown, some investigators suggest that infection with Chlamydia pneumoniae may be a contributing factor. 6 The important role of vascular DCs for the immune response in GCA was shown previously in temporal artery-SCID mouse chimeras. Whereas stimulation of vascular myeloid DCs with lipopolysaccharide (via TLR-4) led to a significant recruitment of activated CD4+ T cells in the adventitia, 7 specific suppression of myeloid DCs using an anti-CD83 antibody completely abrogated vascular inflammation in GCA. 3 Recently, Pryshchep et al described a distinct expression pattern of TLR 1 to 9 on myeloid and plasmacytoid DCs dependent on the anatomic localization of the artery. 7 Remarkably, the unique TLR profile of each vascular territory suggests a specialization in immunosensing functions. 7 This fact raises the question whether activation of DC via different TLRs results in a similar or distinct vascular immune response.New data now reported in this issue of …