CARMA3 Mediates Allergic Lung Inflammation in Response to Alternaria Alternata

Overview

Journal Am J Respir Cell Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2018 Jun 30

PMID 29958012

Citations 12

Authors

Benjamin Causton

Ana Pardo-Saganta

Jacob Gillis

Katherine Discipio

Tristan Kooistra

Jayaraj Rajagopal

Ramnik J Xavier

Josalyn L Cho

Benjamin D Medoff

Affiliations

Soon will be listed here.

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.

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