| First Author | Lee S | Year | 2021 |
| Journal | JCI Insight | Volume | 6 |
| Issue | 16 | PubMed ID | 34423792 |
| Mgi Jnum | J:313000 | Mgi Id | MGI:6792994 |
| Doi | 10.1172/jci.insight.139190 | Citation | Lee S, et al. (2021) Arf6 exacerbates allergic asthma through cell-to-cell transmission of ASC inflammasomes. JCI Insight 6(16) |
| abstractText | 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-1beta production. OVA-induced allergic asthma and associated IL-1beta production were alleviated in mice with small GTPase Arf6-deficient macrophages. The extracellular ASC specks were slightly engulfed by Arf6-/- macrophages, and the IL-1beta 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. |
