期刊
JCI INSIGHT
卷 6, 期 16, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.139190
关键词
-
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [19K16665, 21K06146, 16H05192, 19H03475]
- Japan Agency for Medical Research and Development [JP20fk0108076h0003, JP20wm0325019h0001]
- Japan Science and Technology Agency [JPMJCR20H6, JPMJPF2017]
- Takeda Science Foundation
- NOMURA Microbial Community Control Project in ERATO of Japan Science and Technology Agency
- Grants-in-Aid for Scientific Research [19H03475, 21K06146, 16H05192, 19K16665] Funding Source: KAKEN
Asthma exacerbation is triggered by airway macrophages through a prion-like cell-to-cell transmission of extracellular particulates. Mice with small GTPase Arf6-deficient macrophages show alleviated allergic asthma and reduced IL-1 beta production. The Arf6-dependent intercellular transmission of extracellular ASC specks contributes to the amplification of allergic inflammation and subsequent asthma exacerbation.
Asthma is a chronic inflammatory disease of the airways associated with excess production of Th2 cytokines and lung eosinophil accumulation. This inflammatory response persists in spite of steroid administration that blocks autocrine/paracrine loops of inflammatory cytokines, and the detailed mechanisms underlying asthma exacerbation remain unclear. Here, we show that asthma exacerbation is triggered by airway macrophages through a prion-like cell-to-cell transmission of extracellular particulates, including ASC protein, that assemble inflammasomes and mediate IL-1 beta production. OVA-induced allergic asthma and associated IL-1 beta production were alleviated in mice with small GTPase Arf6-deficient macrophages. The extracellular ASC specks were slightly engulfed by Arf6(-/- )macrophages, and the IL-1 beta production was reduced in Arf6(-/-) macrophages compared with that in WT macrophages. Furthermore, pharmacological inhibition of the Arf6 guanine nucleotide exchange factor suppressed asthma-like allergic inflammation in OVA-challenged WT mice. Collectively, the Arf6-dependent intercellular transmission of extracellular ASC specks contributes to the amplification of allergic inflammation and subsequent asthma exacerbation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据