Granuloma formation in pulmonary sarcoidosis.

Granuloma formation in pulmonary sarcoidosis.
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DOI:
10.3389/fimmu.2013.00437
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发表时间:
2013-12-10
影响因子:
7.3
通讯作者:
van den Blink B
van den Blink B
中科院分区:
医学2区
文献类型:
--
作者:
Broos CE;van Nimwegen M;Hoogsteden HC;Hendriks RW;Kool M;van den Blink B

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结节病是一种原因不明的肉芽肿性疾病,影响多个器官,但主要是肺部。免疫学事件的确切顺序仍然不清楚。回顾现有文献,结合仔细的临床观察,我们提出了一个肺结节病肉芽肿形成的模型。巨噬细胞、树突状细胞和淋巴细胞亚群之间的紧密协作启动了肉芽肿形成的第一步,由细胞因子和趋化因子协调。在相当一部分肺结节病患者中,肉芽肿形成成为一个持续的过程,导致使人衰弱的疾病,有时甚至死亡。决定肉芽肿维持的免疫反应尚不清楚。调节性T细胞的免疫抑制功能受损已被认为是导致过度反应的原因。有趣的是,结节病常用的治疗药物,如糖皮质激素和抗TNF药物,干扰肉芽肿的完整性和恢复自身免疫性疾病的免疫稳态。深入了解其作用机制可能有助于寻找肺结节病的新治疗靶点。
Sarcoidosis is a granulomatous disorder of unknown cause, affecting multiple organs, but mainly the lungs. The exact order of immunological events remains obscure. Reviewing current literature, combined with careful clinical observations, we propose a model for granuloma formation in pulmonary sarcoidosis. A tight collaboration between macrophages, dendritic cells, and lymphocyte subsets, initiates the first steps toward granuloma formation, orchestrated by cytokines and chemokines. In a substantial part of pulmonary sarcoidosis patients, granuloma formation becomes an on-going process, leading to debilitating disease, and sometimes death. The immunological response, determining granuloma sustainment is not well understood. An impaired immunosuppressive function of regulatory T cells has been suggested to contribute to the exaggerated response. Interestingly, therapeutical agents commonly used in sarcoidosis, such as glucocorticosteroids and anti-TNF agents, interfere with granuloma integrity and restore the immune homeostasis in autoimmune disorders. Increasing insight into their mechanisms of action may contribute to the search for new therapeutical targets in pulmonary sarcoidosis.
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