EphA2 phosphorylates NLRP 3 and inhibits inflammasomes in airway epithelial cells
- 30 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Reports
- Vol. 21 (7), e49666
- https://doi.org/10.15252/embr.201949666
Abstract
Inflammasomes are intracellular complexes that form in the cytosol of inflammatory cells. NLRP3 is one of the sensor proteins in the complex that can recognize a wide variety of stimuli ranging from microbial components to environmental particulates. Here, we report that in mouse airway epithelial cells (AECs), inflammasome activation is inhibited by EphA2, a member of the transmembrane tyrosine kinase receptor family, via tyrosine phosphorylation of NLRP3 in a model of reovirus infection. We find that EphA2 depletion markedly enhances interleukin‐1β (IL‐1β) and interleukin‐18 (IL‐18) production in response to the virus. EphA2−/− mice show stronger inflammatory infiltration and enhanced inflammasome activation upon viral infection, and aggravated asthma symptoms upon ovalbumin (ova) induction. Mechanistically, EphA2 binds to NLRP3 and induces its phosphorylation at Tyr132, thereby interfering with ASC speck formation and blocking the activation of the NLRP3‐inflammasome. These data demonstrate that reovirus employs EphA2 to suppress inflammasome activation in AECs and that EphA2 deficiency causes a pathological exacerbation of asthma in an ova‐induced asthma model.Keywords
Funding Information
- National Natural Science Foundation of China (81520108022, 81621004, 81830090)
- National Institute of Allergy and Infectious Diseases (R01AI080779)
- Lupus Research Alliance (519418)
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