{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T05:28:52Z","timestamp":1778563732809,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,6]],"date-time":"2018-09-06T00:00:00Z","timestamp":1536192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["VO944\/9\u20101"],"award-info":[{"award-number":["VO944\/9\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Eosinophils are innate effector cells associated with allergic inflammation. Their development and survival is largely dependent on IL\u20105 and the common beta chain (\u03b2<jats:sub>c<\/jats:sub>) of the IL\u20105 receptor that serves as docking site for several proteins that mediate down\u2010stream signaling cascades including JAK\/STAT, PI3 kinase, NF\u03baB, and RAS\u2010MAP kinase pathways. The relative contribution of these signaling pathways for eosinophil development and homeostasis in vivo are poorly understood. Here, we investigated the role of GRB2, an adaptor protein that binds to \u03b2<jats:sub>c<\/jats:sub> and other proteins and elicits the RAS\u2010MAP kinase pathway. By using GRB2 inhibitors and inducible deletion of the <jats:italic>Grb2<\/jats:italic> gene in mouse eosinophils we demonstrate that GRB2 plays a critical role for development of eosinophils from bone marrow precursors. Furthermore, <jats:italic>Aspergillus fumigatus<\/jats:italic>\u2010induced allergic lung eosinophilia was significantly reduced in mice with induced genetic deletion of <jats:italic>Grb2<\/jats:italic>. Our results indicate that GRB2 is important for eosinophil development in steady\u2010state conditions and during allergic inflammation. Based on these findings pharmacologic GRB2 inhibitors may have the potential to dampen tissue eosinophilia in various eosinophil\u2010associated diseases.<\/jats:p>","DOI":"10.1002\/eji.201847555","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T10:56:18Z","timestamp":1536144978000},"page":"1786-1795","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Murine eosinophil development and allergic lung eosinophilia are largely dependent on the signaling adaptor GRB2"],"prefix":"10.1002","volume":"48","author":[{"given":"Ralf","family":"Willebrand","sequence":"first","affiliation":[{"name":"Department of Infection Biology University Hospital Erlangen and Friedrich\u2010Alexander University Erlangen\u2010Nuremberg (FAU)  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Dietschmann","sequence":"additional","affiliation":[{"name":"Department of Infection Biology University Hospital Erlangen and Friedrich\u2010Alexander University Erlangen\u2010Nuremberg (FAU)  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7236-379X","authenticated-orcid":false,"given":"Lars","family":"Nitschke","sequence":"additional","affiliation":[{"name":"Department of Biology Friedrich\u2010Alexander University Erlangen\u2010Nuremberg (FAU)  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Krappmann","sequence":"additional","affiliation":[{"name":"Institute for Clinical Microbiology, Hygiene and Immunology University Hospital Erlangen and Friedrich\u2010Alexander University Erlangen\u2010Nuremberg (FAU)  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6650-0639","authenticated-orcid":false,"given":"David","family":"Voehringer","sequence":"additional","affiliation":[{"name":"Department of Infection Biology University Hospital Erlangen and Friedrich\u2010Alexander University Erlangen\u2010Nuremberg (FAU)  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,9,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.95"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1981"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.02.014"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1201475"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1304046110"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.053"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.066"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3159"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1393134"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161070"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.5.1425"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.163.5.1085"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80294-0"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90046-2"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.21.9565"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(98)00023-0"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-10-607788"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.21.12137"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/363083a0"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81702-X"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.13.7776"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.9.1791"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.4.561"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.74"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2757"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.03.024"},{"key":"e_1_2_7_28_1","first-page":"544","article-title":"Sclerotiorin and isochromophilone IV: inhibitors of Grb2\u2010Shc interaction, isolated from penicillium multicolor F1753","volume":"10","author":"Nam J.\u2010Y.","year":"2000","journal-title":"J. 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