{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T05:44:44Z","timestamp":1771911884933,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,1,4]],"date-time":"2019-01-04T00:00:00Z","timestamp":1546560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2015R1A2A2A05001024"],"award-info":[{"award-number":["2015R1A2A2A05001024"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2014R1A4A1071040"],"award-info":[{"award-number":["2014R1A4A1071040"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nuclear receptor subfamily 4 group A member 1 (NR4A1), an orphan nuclear receptor, has been implicated in several biological events such as metabolism, apoptosis, and inflammation. Recent studies indicate a potential role for NR4A1 in mast cells, yet its role in allergic responses remains largely unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim of this study was to clarify the role of NR4A1 in mast cell activation and anaphylaxis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To evaluate the function of NR4A1 in mast cells, the impacts of siRNA knockdown, gene knockout, adenoviral overexpression, and pharmacological inhibition of NR4A1 on Fc\u03b5RI signaling and effector functions in mouse bone marrow\u2013derived mast cells (BMMCs) in\u00a0vitro and on anaphylactic responses in\u00a0vivo were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Knockdown or knockout of NR4A1 markedly suppressed degranulation and lipid mediator production by Fc\u03b5RI\u2010crosslinked BMMCs, while its overexpression augmented these responses. Treatment with a NR4A1 antagonist also blocked mast cell activation to a similar extent as NR4A1 knockdown or knockout. Moreover, mast cell\u2013specific NR4A1\u2010deficient mice displayed dampened anaphylactic responses in\u00a0vivo. Mechanistically, NR4A1 promoted Fc\u03b5RI signaling by counteracting the liver kinase B1 (LKB1)\/adenosine monophosphate\u2010activated protein kinase (AMPK) axis. Following Fc\u03b5RI crosslinking, NR4A1 bound to the LKB1\/AMPK complex and sequestered it in the nucleus, thereby promoting Fc\u03b5RI downstream signaling pathways. Silencing or knockout of LKB1\/AMPK largely abrogated the effect of NR4A1 on mast cell activation. Additionally, NR4A1 facilitated spleen tyrosine kinase activation independently of LKB1\/AMPK.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Nuclear receptor subfamily 4 group A member 1 positively regulates mast cell activation by antagonizing the LKB1\u2010AMPK\u2010dependent negative regulatory axis. This finding may provide a novel therapeutic strategy for the development of anti\u2010allergic compounds.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13702","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T10:58:39Z","timestamp":1545217119000},"page":"1145-1156","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The orphan nuclear receptor NR4A1 promotes Fc\u03b5RI\u2010stimulated mast cell activation and anaphylaxis by counteracting the inhibitory LKB1\/AMPK axis"],"prefix":"10.1111","volume":"74","author":[{"given":"Fansi","family":"Jin","sequence":"first","affiliation":[{"name":"College of Pharmacy Yeungnam University Gyeongsan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy Yeungnam University Gyeongsan 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