Increased inflammasome related gene expression profile in PBMC may facilitate T helper 17 cell induction in multiple sclerosis
Increased inflammasome related gene expression profile in PBMC may facilitate T helper 17 cell induction in multiple sclerosis
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DOI：
10.1016/j.molimm.2014.10.008
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发表时间：
2015-02-01
影响因子：
3.6
通讯作者：
Thewissen, M.
中科院分区：
文献类型：
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作者：
Peelen, E.;Damoiseaux, J.;Thewissen, M.
NLRP3 炎症小体是一种重要参与 IL-1 β 加工的大分子复合物。其在多发性硬化症 (MS) 中的作用已被描述。 IL-1β 可能参与 MS 的一种机制是诱导致病性 Th17 细胞，即 GM-CSF+ Th17 细胞。在本研究中，我们发现，与健康对照 (HC) 相比，MS 患者的 PBMC 中炎症体相关基因、NLRP3、caspase-1、IL-1 beta 和 IL-1 beta/IL-1Ra 比率的表达增加。然而，在 PBMC 体外炎症小体活性测定中，MS 患者和 HC 患者的 IL-1 β 蛋白分泌和 IL-1 β/IL-1Ra 蛋白比率相似。与在对照上清液存在下培养的 Th 细胞相比，在存在 LPS/ATP 炎性体激活的 PBMC 的上清液存在下培养的 Th 细胞显示，HC 和 MS 患者中 Th17 和 GM-CSF+ Th17 细胞频率增加，而 HC 患者中抗炎 IL-10(+)Th 细胞频率降低。此外，在前一种条件中添加免疫调节剂骨化三醇导致Th17和GM-CSF(+)Th17细胞以及IL-10(+) Th细胞的频率降低。显然，我们的数据表明，炎症小体活动可以使 Th 细胞群偏向于更具促炎性的成分，这种作用可能会被维生素 D 抑制，并且可能与中枢神经系统内的炎症有关。 (C) 2014 Elsevier Ltd. 保留所有权利。
The NLRP3 inflammasome is a macromolecular complex importantly involved in IL-1 beta processing. A role for this has been described in multiple sclerosis (MS). One mechanism by which IL-1 beta might be involved in MS is by inducing pathogenic Th17 cells, i.e. GM-CSF+ Th17 cells. In the present study, we show that expression of the inflammasome related genes, NLRP3, caspase-1, IL-1 beta and the IL-1 beta/IL-1Ra ratio, was increased in PBMC from MS patients compared to healthy controls (HC). However, in an in vitro inflammasome activity assay with PBMC, IL-1 beta protein secretion and the IL-1 beta/IL-1Ra protein ratio were similar in MS patients and HC. Th cells cultured in the presence of supernatant derived from LPS/ATP inflammasome activated PBMC showed increased Th17 and GM-CSF+ Th17 cell frequencies in HC and MS patients and decreased anti-inflammatory IL-10(+)Th cell frequency in HC compared to Th cells cultured in the presence of control supernatant. Moreover, addition of the immune modulator calcitriol to the former condition resulted in reduced frequencies of Th17 and GM-CSF(+)Th17 cells, and also of IL-10(+) Th cells. Evidently, our data indicate that inflammasome activity can skew the Th cell population toward a more pro-inflammatory composition, an effect that might be inhibited by vitamin D, and that might be importantly involved in inflammation within the central nervous system. (C) 2014 Elsevier Ltd. All rights reserved.