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EphA2 phosphorylates NLRP 3 and inhibits inflammasomes in airway epithelial cells
Author(s) -
Zhang Ao,
Xing Junji,
Xia Tianliang,
Zhang Hua,
Fang Mingli,
Li Shibing,
Du Yong,
Li Xian C,
Zhang Zhiqiang,
Zeng MuSheng
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949666
Subject(s) - inflammasome , phosphorylation , ovalbumin , microbiology and biotechnology , tyrosine phosphorylation , biology , chemistry , immunology , inflammation , immune system
Inflammasomes are intracellular complexes that form in the cytosol of inflammatory cells. NLRP 3 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 ( AEC s), inflammasome activation is inhibited by EphA2, a member of the transmembrane tyrosine kinase receptor family, via tyrosine phosphorylation of NLRP 3 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 NLRP 3 and induces its phosphorylation at Tyr132, thereby interfering with ASC speck formation and blocking the activation of the NLRP 3‐inflammasome. These data demonstrate that reovirus employs EphA2 to suppress inflammasome activation in AEC s and that EphA2 deficiency causes a pathological exacerbation of asthma in an ova‐induced asthma model.