{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:21:54Z","timestamp":1771546914324,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T00:00:00Z","timestamp":1541980800000},"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":["KO1245\/3\u20101"],"award-info":[{"award-number":["KO1245\/3\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004168","name":"Universit\u00e4t zu L\u00fcbeck","doi-asserted-by":"publisher","award":["J10\u20102016"],"award-info":[{"award-number":["J10\u20102016"]}],"id":[{"id":"10.13039\/501100004168","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2019,4]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Food\u2010induced anaphylaxis is a serious allergic reaction caused by Fc\u03b5\u2010receptor activation on mast cells (MC<\/jats:styled-content>s). The exact mechanisms breaking oral tolerance and the effector pathways driving food allergy remain elusive. As complement is activated in food\u2010induced anaphylaxis, we aimed to assess the role of C5a in disease pathogenesis.<\/jats:p><\/jats:sec>Methods<\/jats:title>Oral antigen\u2010induced food\u2010induced anaphylaxis was induced in BALB<\/jats:styled-content>\/c wild\u2010type (wt) and C5ar1<\/jats:italic>\u2212\/\u2212<\/jats:sup> mice. Readouts included diarrhea development, changes in rectal temperature, hematocrit, antigen\u2010specific serum IgE, MCPT<\/jats:styled-content>\u20101, and intestinal MC<\/jats:styled-content> numbers, as well as Fc\u03b5R1\u2010mediated MC<\/jats:styled-content> functions including C5a receptor 1 (C5aR1) regulation. Further, histamine\u2010mediated hypothermia and regulation of endothelial tight junctions were determined.<\/jats:p><\/jats:sec>Results<\/jats:title>Repeated oral OVA<\/jats:styled-content> challenge resulted in diarrhea, hypothermia, increased hematocrit, high OVA<\/jats:styled-content>\u2010specific serum IgE, and MCPT<\/jats:styled-content>\u20101 levels in wt mice. Male C5ar1<\/jats:italic>\u2212\/\u2212<\/jats:sup> mice were completely whereas female C5ar1<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice were partially protected from anaphylaxis development. Serum MCPT<\/jats:styled-content>\u20101 levels were reduced gender\u2010independent, whereas IgE levels were reduced in male but not in female C5ar1<\/jats:italic>\u2212\/\u2212<\/jats:sup> mice. Mechanistically, IgE\u2010mediated degranulation and IL<\/jats:styled-content>\u20106 production from C5ar1<\/jats:italic>\u2212\/\u2212<\/jats:sup> BMMC<\/jats:styled-content>s of both sexes were significantly reduced. Importantly, Fc\u03b5R1 cross\u2010linking strongly upregulated C5aR1 MC<\/jats:styled-content> expression in vitro and in vivo. Finally, C5ar1<\/jats:italic>\u2212\/\u2212<\/jats:sup> male mice were largely protected from histamine\u2010induced hypovolemic shock, which was associated with protection from histamine\u2010induced barrier dysfunction in vitro following C5aR targeting.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Our findings identify C5aR1 activation as an important driver of IgE\u2010mediated food allergy through regulation of allergen\u2010specific IgE production, Fc\u03b5R1\u2010mediated MC<\/jats:styled-content> degranulation, and histamine\u2010driven effector functions preferentially in male mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13637","type":"journal-article","created":{"date-parts":[[2018,10,20]],"date-time":"2018-10-20T05:28:33Z","timestamp":1540013313000},"page":"767-779","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["C5a receptor 1\u2212\/\u2212<\/sup> mice are protected from the development of IgE\u2010mediated experimental food allergy"],"prefix":"10.1111","volume":"74","author":[{"given":"Anna","family":"Kordowski","sequence":"first","affiliation":[{"name":"Institute for Systemic Inflammation Research University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna T.","family":"Reinicke","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology Cincinnati Children's Hospital and University of Cincinnati College of Medicine Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zane","family":"Orinska","sequence":"additional","affiliation":[{"name":"Division of Experimental Pneumology Research Center Borstel Leibniz Lung Center Borstel Germany"},{"name":"Airway Research Center North (ARCN) German Center for Lung Research (DZL) Borstel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Hagemann","sequence":"additional","affiliation":[{"name":"Division of Experimental Pneumology Research Center Borstel Leibniz Lung Center Borstel Germany"},{"name":"Airway Research Center North (ARCN) German Center for Lung Research (DZL) Borstel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Huber\u2010Lang","sequence":"additional","affiliation":[{"name":"Institute of Clinical and Experimental Trauma\u2010Immunology University Hospital of Ulm Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jee\u2010Boong","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology Cincinnati Children's Hospital and University of Cincinnati College of Medicine Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yui\u2010Hsi","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology Cincinnati Children's Hospital and University of Cincinnati College of Medicine Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon P.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology Cincinnati Children's Hospital and University of Cincinnati College of Medicine Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1121-3178","authenticated-orcid":false,"given":"J\u00f6rg","family":"K\u00f6hl","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research University of L\u00fcbeck L\u00fcbeck Germany"},{"name":"Airway Research Center North (ARCN) German Center for Lung Research (DZL) Borstel Germany"},{"name":"Division of Immunobiology Cincinnati Children's Hospital and University of Cincinnati College of Medicine Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.07.004"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.06.015"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.11.004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.05.009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27659"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85538"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.8.2863"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401401"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.12.036"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-12-14"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.7.3835"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906372106"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26907-2"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80204-6"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13013"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI19785"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.08.020"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000892"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804276"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071046"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64461-6"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310078200"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.214965"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.01.034"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2003.01571.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.06.003"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.125977"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302417"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500535200"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2015.0099"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.23.13430"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2013.04.009"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.2.411"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110159"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.11.021"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3038.2008.00792.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1210"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.4.1693"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00119"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)43936-1"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI16577"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800498200"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2013.06.016"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25536"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2862"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.119"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0525-17.2017"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2013.0318"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.11.003"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.04.011"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00039-3"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490010504"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00372-8"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(00)00304-0"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2009.03374.x"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-012-0320-1"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.4.1861"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fall.13637","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.13637","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/all.13637","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.13637","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T19:44:59Z","timestamp":1694375099000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.13637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,12]]},"references-count":57,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1111\/all.13637"],"URL":"https:\/\/doi.org\/10.1111\/all.13637","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,12]]},"assertion":[{"value":"2018-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}