Journal article
CARMA3 Mediates Allergic Lung Inflammation in Response to Alternaria alternata
American journal of respiratory cell and molecular biology, Vol.59(6), pp.684-694
12/2018
DOI: 10.1165/rcmb.2017-0181OC
PMCID: PMC6293075
PMID: 29958012
Abstract
The airway epithelial cell (AEC) response to allergens helps initiate and propagate allergic inflammation in asthma. CARMA3 is a scaffold protein that mediates G protein-coupled receptor-induced NF-κB activation in airway epithelium. In this study, we demonstrate that mice with CARMA3-deficient AECs have reduced airway inflammation, as well as reduced type 2 cytokine levels in response to Alternaria alternata. These mice also have reduced production of IL-33 and IL-25, and reduced numbers of innate lymphoid cells in the lung. We also show that CARMA3-deficient human AECs have decreased production of proasthmatic mediators in response to A. alternata. Finally, we show that CARMA3 interacts with inositol 1,4,5-trisphosphate receptors in AECs, and that inhibition of CARMA3 signaling reduces A. alternata-induced intracellular calcium release. In conclusion, we show that CARMA3 signaling in AECs helps mediate A. alternata-induced allergic airway inflammation, and that CARMA3 is an important signaling molecule for type 2 immune responses in the lung.
Details
- Title: Subtitle
- CARMA3 Mediates Allergic Lung Inflammation in Response to Alternaria alternata
- Creators
- Benjamin Causton - Division of Pulmonary and Critical Care Medicine, Center for Regenerative MedicineAna Pardo-Saganta - Division of Pulmonary and Critical Care Medicine, Center for Computational and Integrative Biology, andJacob Gillis - Division of Pulmonary and Critical Care Medicine, Center for Regenerative MedicineKatherine Discipio - Division of Pulmonary and Critical Care Medicine, Center for Regenerative MedicineTristan Kooistra - Division of Pulmonary and Critical Care Medicine, Center for Regenerative MedicineJayaraj Rajagopal - Division of Pulmonary and Critical Care Medicine, Center for Computational and Integrative Biology, andRamnik J Xavier - Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MassachusettsJosalyn L Cho - Division of Pulmonary and Critical Care Medicine, Center for Regenerative MedicineBenjamin D Medoff - Division of Pulmonary and Critical Care Medicine, Center for Regenerative Medicine
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.59(6), pp.684-694
- DOI
- 10.1165/rcmb.2017-0181OC
- PMID
- 29958012
- PMCID
- PMC6293075
- NLM abbreviation
- Am J Respir Cell Mol Biol
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Language
- English
- Date published
- 12/2018
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094504102771
Metrics
21 Record Views