Journal article
NLRP1 variant M1184V decreases inflammasome activation in the context of DPP9 inhibition and asthma severity
J Moecking, P Laohamonthonkul, K Chalker, MJ White, CR Harapas, CH Yu, S Davidson, K Hrovat-Schaale, D Hu, C Eng, S Huntsman, DJ Calleja, JC Horvat, PM Hansbro, RJJ O'Donoghue, JP Ting, EG Burchard, M Geyer, M Gerlic, SL Masters
Journal of Allergy and Clinical Immunology | MOSBY-ELSEVIER | Published : 2021
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) individ..
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Awarded by Sandler Foundation
Funding Acknowledgements
We thank R. Crawley and S. Russo for outstanding animal husbandry. We also acknowledge the Trans-Omics in Precision Medicine (TOPMed) program imputation panel (freeze 5) supported by the National Heart, Lung, and Blood Institute accessed through the Michigan Imputation Server. The panel was constructed and implemented by the TOPMed Informatics Research Center at the University of Michigan (3R01HL-117626-02S1; contract HHSN268201800002I). The TOPMed Data Coordinating Center (3R01HL-120393-02S1; contract HHSN268201800001I) provided additional data management, sample identity checks, and overall program coordination and support. The Graphical Abstract was prepared using Biorender. We gratefully acknowledge the studies and participants who provided biological samples and data for TOPMed.