@article{240fca7c3383446c92c675c16c01919d,
title = "EphA2 phosphorylates NLRP3 and inhibits inflammasomes in airway epithelial cells",
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 = "EphA2, NLRP3, asthma, inflammasome, reovirus",
author = "Ao Zhang and Junji Xing and Tianliang Xia and Hua Zhang and Mingli Fang and Shibing Li and Yong Du and Li, {Xian C} and Zhiqiang Zhang and Mu-Sheng Zeng",
note = "Funding Information: We thank Laurie Minze at Houston Methodist Research Institute for her excellent operational support. We thank our language editor Mr. Christopher Lavender of Sun Yat‐sen University Cancer Center for providing assistance in editing this manuscript. M.Z. is supported by the National Key Research and Development Program of China (2017YFA0505600, 2017YFC0908503, and 2016YFA0502100), the National Natural Science Foundation of China (81520108022, 81621004, and 81830090), and the Guangdong Province Key Research and Development Program (2019B020226002). XCL is supported by the National Institutes of Health grant R01AI080779. Z.Z. is supported by the Lupus Research Alliance Grant 519418. Funding Information: We thank Laurie Minze at Houston Methodist Research Institute for her excellent operational support. We thank our language editor Mr. Christopher Lavender of Sun Yat-sen University Cancer Center for providing assistance in editing this manuscript. M.Z. is supported by the National Key Research and Development Program of China (2017YFA0505600, 2017YFC0908503, and 2016YFA0502100), the National Natural Science Foundation of China (81520108022, 81621004, and 81830090), and the Guangdong Province Key Research and Development Program (2019B020226002). XCL is supported by the National Institutes of Health grant R01AI080779. Z.Z. is supported by the Lupus Research Alliance Grant 519418. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = jul,
day = "3",
doi = "10.15252/embr.201949666",
language = "English (US)",
volume = "21",
pages = "e49666",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "7",
}