CARD9S12N facilitates the production of IL-5 by alveolar macrophages for the induction of type 2 immune responses

Nature Immunology
Xia XuXin Lin

Abstract

The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the TH1 and TH17 subsets of helper T cells. The single-nucleotide polymorphism rs4077515 at CARD9 in the human genome, which results in the substitution S12N (CARD9S12N), is associated with several autoimmune diseases. However, the function of CARD9S12N has remained unknown. Here we generated CARD9S12N knock-in mice and found that CARD9S12N facilitated the induction of type 2 immune responses after engagement of CLRs. Mechanistically, CARD9S12N mediated CLR-induced activation of the non-canonical transcription factor NF-κB subunit RelB, which initiated production of the cytokine IL-5 in alveolar macrophages for the recruitment of eosinophils to drive TH2 cell-mediated allergic responses. We identified the homozygous CARD9 mutation encoding S12N in patients with allergic bronchopulmonary aspergillosis and revealed activation of RelB and production of IL-5 in peripheral blood mononuclear cells from these patients. Our study provides genetic and functional evidence demonstrating that CARD9S12N can turn alveolar macrophages into IL-5-producing cells and facilitates TH2 cell-mediated pathologic...Continue Reading

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Citations

Nov 24, 2018·Nature Reviews. Immunology·Jürgen Ruland, Lara Hartjes
Nov 2, 2019·Ocular Immunology and Inflammation·Fuzhen LiPeizeng Yang
Oct 28, 2019·Alimentary Pharmacology & Therapeutics·Siu LamSiew C Ng
Feb 28, 2020·Nature·Daniel B Graham, Ramnik J Xavier
Nov 15, 2019·Clinical Microbiology Reviews·Jean-Paul Latgé, Georgios Chamilos
Mar 10, 2020·Gut Microbes·Di ZhangTingting Wang
Aug 22, 2018·Frontiers in Immunology·Rebecca A DrummondMichail S Lionakis
Jan 26, 2021·Mediators of Inflammation·Ruanmei ShengXuemin Wang
Jan 17, 2021·The Journal of Allergy and Clinical Immunology·Yael Renert-YuvalAmy S Paller
Mar 1, 2021·Signal Transduction and Targeted Therapy·Zhou YuXuetao Cao
Mar 15, 2021·Current Opinion in Immunology·Henry Y Lu, Stuart E Turvey

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Methods Mentioned

BETA
PCR
ELISA
flow cytometry
Flow
nuclear translocation
immunoprecipitation
genotyping
ChIP
transfection

Software Mentioned

FlowJo
GraphPad Prism
IDEAS
Ensembl
Polyphen
ImageStream IDEAS

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Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.