Unknown

Dataset Information

0

Arf6 exacerbates allergic asthma through cell-to-cell transmission of ASC inflammasomes.


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.

SUBMITTER: Lee S 

PROVIDER: S-EPMC8410019 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC3098800 | biostudies-other
| S-EPMC7581806 | biostudies-literature
| S-EPMC4324825 | biostudies-literature
| S-EPMC8455077 | biostudies-literature
| S-EPMC4000066 | biostudies-literature
| S-EPMC8410088 | biostudies-literature
| S-EPMC4917984 | biostudies-literature
| S-EPMC7336542 | biostudies-literature
| S-EPMC4716619 | biostudies-other
| S-EPMC5073040 | biostudies-literature