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首页> 外文期刊>American Journal of Physiology >Elevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes
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Elevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes

机译：肺病变肺中的IL-15浓度均独立于肉芽肿负担和疾病表型

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摘要

Sarcoidosis is a systemic granulomatous disease predominantly affecting the lungs. The mechanisms promoting disease patho-genesis and progression are unknown, although interleukin-15 (IL-15) has been associated with the immune-mediated inflammation of sarcoidosis. Because the identification of a mechanistically based, clinically relevant biomarker for sarcoidosis remains elusive, we hypothesized this role for IL-15. Pulmonary sarcoidosis granuloma formation was modeled using trehalose 6,6'-dimi-colate (TDM), which was administered into wild-type and three lineages of mice: those overexpressing IL-15, deficient in IL-15, and deficient in IL-15 receptor a. The number of granulomas per lung was counted and normalized to the wild type. IL-15 concentrations were measured in the bronchoalveolar lavage (BAL) from healthy controls and subjects with sarcoidosis in our cohort, where associations between IL-15 levels and clinical manifestations were sought. Findings were validated in another independent sarcoidosis cohort. TDM administration resulted in similar granuloma numbers across all lineages of mice. IL-15 concentrations were elevated in the BAL of both human cohorts, irrespective of disease phenotypes. In exploratory analysis, an association with obesity was observed, and various other soluble mediators were identified in the BAL of both cohorts. Although IL-15 is enriched in the sarcoidosis lung, it was independent of disease pathogenesis or clinical manifestations in our mouse model and human cohorts of sarcoidosis. An association with obesity perhaps reflects the ongoing inflammatory processes of these comorbid conditions. Our findings showed that IL-15 is redundant for disease pathogenesis and clinical progression of sarcoidosis.
机译：结节病是一种主要影响肺部的全身肉芽肿性疾病。尽管白细胞介素-15（IL-15）与免疫介导的结节病炎症有关，但促进疾病病理发生和进展的机制尚不清楚。由于结节病的机制性、临床相关生物标志物的鉴定仍然难以捉摸，我们假设IL-15发挥这种作用。肺结节病肉芽肿的形成是用海藻糖6,6'-dimi-colate（TDM）来模拟的，它被注射到野生型和三个谱系的小鼠中：过度表达IL-15、缺乏IL-15和缺乏IL-15受体a的小鼠。计算每个肺的肉芽肿数量，并将其标准化为野生型。在我们的队列研究中，从健康对照组和结节病受试者的支气管肺泡灌洗液（BAL）中测量IL-15浓度，寻找IL-15水平与临床表现之间的关联。研究结果在另一个独立结节病队列中得到验证。TDM给药导致所有小鼠谱系的肉芽肿数量相似。无论疾病表型如何，两组人群的BAL中IL-15浓度均升高。在探索性分析中，观察到与肥胖相关，并在两个队列的BAL中确定了各种其他可溶性介质。虽然IL-15在结节病肺中富集，但在我们的小鼠模型和人类结节病队列中，它与疾病发病机制或临床表现无关。与肥胖的关联可能反映了这些共病的持续炎症过程。我们的研究结果表明，IL-15在结节病的发病机制和临床进展中是多余的。

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