NLRP1 variant M1184V decreases inflammasome activation in the context of DPP9 inhibition and asthma severity.

ABSTRACT:

Background

NLRP1 is an innate immune sensor that can form cytoplasmic inflammasome complexes. Polymorphisms in NLRP1 are linked to asthma; however, there is currently no functional or mechanistic explanation for this.

Objective

We sought to clarify the role of NLRP1 in asthma pathogenesis.

Methods

Results from the GALA II cohort study were used to identify a link between NLRP1 and asthma in Mexican Americans. In vitro and in vivo models for NLRP1 activation were applied to investigate the role of this inflammasome in asthma at the molecular level.

Results

We document the association of an NLRP1 haplotype with asthma for which the single nucleotide polymorphism rs11651270 (M1184V) individually is the most significant. Surprisingly, M1184V increases NLRP1 activat

SUBMITTER: Moecking J 

PROVIDER: S-EPMC8168955 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature