論文 - 詳細
| RRC ID | 68101 |
|---|---|
| 著者 | Lee S, Ishitsuka A, Kuroki T, Lin YH, Shibuya A, Hongu T, Funakoshi Y, Kanaho Y, Nagata K, Kawaguchi A. |
| タイトル | Arf6 exacerbates allergic asthma through cell-to-cell transmission of ASC inflammasomes. |
| ジャーナル | JCI Insight |
| Abstract |
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-1β production. OVA-induced allergic asthma and associated IL-1β production were alleviated in mice with small GTPase Arf6-deficient macrophages. The extracellular ASC specks were slightly engulfed by Arf6-/- macrophages, and the IL-1β 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. |
| 巻・号 | 6(16) |
| 公開日 | 2021-8-23 |
| DOI | 10.1172/jci.insight.139190 |
| PII | e139190 |
| PMID | 34423792 |
| PMC | PMC8410019 |
| MeSH | ADP-Ribosylation Factor 6 / antagonists & inhibitors ADP-Ribosylation Factor 6 / genetics ADP-Ribosylation Factor 6 / metabolism* Animals Asthma / drug therapy Asthma / immunology* Asthma / pathology CARD Signaling Adaptor Proteins / metabolism Cell Communication / drug effects Cell Communication / immunology* Disease Models, Animal Humans Inflammasomes / drug effects Inflammasomes / immunology* Inflammasomes / metabolism Interleukin-1beta / metabolism Lung / immunology Lung / pathology Macrophages, Alveolar / immunology* Macrophages, Alveolar / metabolism Mice Mice, Knockout Ovalbumin / administration & dosage Ovalbumin / immunology Phagocytosis / drug effects Symptom Flare Up THP-1 Cells Th2 Cells Triazoles / administration & dosage |
| IF | 6.205 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |