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I型干扰素调节人体巨细胞中互白素-1β和IL-18的产生和分泌

Rodrigo Díaz-Pino^1,2, Gillian I Rice^3,4, Diego San Felipe^1,2,5

¹Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.

Life science alliance

|March 25, 2024

概括

I型干扰素 (IFN) 影响炎症体活动,影响炎症性细胞因子的释放. 这项研究发现,IFN-α增加了炎症体基因表达,但减少了成熟的IL-1β和IL-18释放,这表明了复杂的调节机制.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
遗传学遗传学是一个

背景情况:

炎症体是关键的免疫复合体,释放出促炎细胞因子IL-18和IL-1β.
第一种类型的IFN对通过IFN刺激基因 (ISG) 的抗病毒反应和炎症至关重要.
第一种类型的IFN和炎症体之间的调节相互作用尚未得到充分理解.

研究的目的:

调查I型IFN对炎症体基因表达和细胞因子释放的影响.
分析来自单一性干涉病患者的RNA测序数据,以检测炎症组基因变异.
阐明IFN-α对炎症酶激活的调节机制.

主要方法:

分析来自单一性干扰性疾病患者的RNA测序数据.
用IFN-α治疗人类单细胞衍生的巨细胞.
测量与炎症酶相关的基因mRNA水平 (CASP1,GSDMD,IL1B,NLRP3) 的测量.
在ATP介导的NLRP3炎症酶激活后,对成熟的IL-1β和IL-18释放的评估.

主要成果:

在患有单一性干扰性疾病的患者中观察到几个与炎症体相关的基因的上调.
随着时间的推移,IFN-α治疗增加了巨细胞中的CASP1和GSDMDmRNA水平.
IFN-α治疗降低了成熟的IL-1β和IL-18释放,但没有降低酶-1活性.
IL1B和NLRP3mRNA水平与IFN-α暴露时间没有直接相关.

结论:

第一种类型的IFN,特别是IFN-α,会影响炎症体基因表达,上调CASP1和GSDMD.
似乎IFN-α在细胞因子表达水平上调节炎酶体功能,而不是炎酶体复合体本身.
需要进一步的研究,以充分了解IFN-α的炎症体的转录和后翻译调节.

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