T cell-macrophage interactions and granuloma formation in vasculitis.
T cell-macrophage interactions and granuloma formation in vasculitis.
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DOI：
10.3389/fimmu.2014.00432
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发表时间：
2014
影响因子：
7.3
通讯作者：
Weyand CM
中科院分区：
文献类型：
--
作者：
Hilhorst M;Shirai T;Berry G;Goronzy JJ;Weyand CM
肉芽肿形成是炎症性血管疾病中的一种典型事件，它使高活性的巨噬细胞和T细胞接近，并以几种血管炎的名义出现。目前尚不清楚血管壁或血管周围微环境的特定性质是否有助于肉芽肿的形成，在某些情况下，还会导致多核巨细胞的产生。肉芽肿为优化巨噬细胞-T细胞的相互作用提供了专门的利基，强烈激活了这两种细胞类型。这反映在脉管炎患者遇到的全身炎症的强度上，通常表现为不适、体重减轻、发热和强烈上调的急性时相反应。肉芽肿是一种高度组织化的复杂结构，是诱导T细胞分化成熟的理想场所。肉芽肿可能导致异常的Th1和Th17细胞进入循环，这两种细胞被认为是血管炎的主要致病细胞。通过诱导记忆T细胞，异常的先天免疫反应可以在未来几十年内印记宿主免疫系统，并促进疾病过程的慢性化。提高对T细胞-巨噬细胞相互作用的了解将重新定义血管炎的致病模型，并为免疫调节治疗提供新的途径。
Granuloma formation, bringing into close proximity highly activated macrophages and T cells, is a typical event in inflammatory blood vessel diseases, and is noted in the name of several of the vasculitides. It is not known whether specific properties of the microenvironment in the blood vessel wall or the immediate surroundings of blood vessels contribute to granuloma formation and, in some cases, generation of multinucleated giant cells. Granulomas provide a specialized niche to optimize macrophage–T cell interactions, strongly activating both cell types. This is mirrored by the intensity of the systemic inflammation encountered in patients with vasculitis, often presenting with malaise, weight loss, fever, and strongly upregulated acute phase responses. As a sophisticated and highly organized structure, granulomas can serve as an ideal site to induce differentiation and maturation of T cells. The granulomas possibly seed aberrant Th1 and Th17 cells into the circulation, which are known to be the main pathogenic cells in vasculitis. Through the induction of memory T cells, aberrant innate immune responses can imprint the host immune system for decades to come and promote chronicity of the disease process. Improved understanding of T cell–macrophage interactions will redefine pathogenic models in the vasculitides and provide new avenues for immunomodulatory therapy.