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Comprehensive knowledge of Fc\u03b5RI regulation is thus required. We have identified a functional interaction between Fc\u03b5RI and CD13 in murine MCs. Antigen\u2010triggered activation of IgE\u2010loaded Fc\u03b5RI results in cocapping and cointernalization of CD13 and equivalent internalization rates of up to 40%. Cointernalization is not unspecific, because ligand\u2010driven KIT internalization is not accompanied by CD13 internalization. Moreover, antibody\u2010mediated cross\u2010linking of CD13 causes IL\u20106 production in an Fc\u03b5RI\u2010dependent manner. These data are indicative of a functional interaction between Fc\u03b5RI and CD13 on MCs. To determine the role of this interaction, CD13\u2010deficient bone marrow\u2010derived MCs (BMMCs) were analyzed. Intriguingly, antigen stimulation of CD13\u2010deficient BMMCs results in significantly increased degranulation and proinflammatory cytokine production compared to wild\u2010type cells. Furthermore, in a low\u2010dose model of passive systemic anaphylaxis, antigen\u2010dependent decrease in body temperature, reflecting the anaphylactic reaction, is substantially enhanced by the CD13 inhibitor bestatin (\u20135.9 \u00b1 0.6\u00b0C) and by CD13 deficiency (\u20138.8 \u00b1 0.6\u00b0C) in contrast to controls (\u20131.2 \u00b1 1.97\u00b0C). Importantly, bestatin does not aggravate anaphylaxis in CD13\u2010deficient mice. Thus, we have identified CD13 as a novel negative regulator of MC activation\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo.<\/jats:italic>\n                    \u2014Zotz, J. S., W\u00f6lbing, F., Lassnig, C., Kauffmann, M., Schulte, U., Kolb, A., Whitelaw, B., M\u00fcller, M., Biedermann, T., Huber, M. CD13\/aminopeptidase N is a negative regulator of mast cell activation. FASEB J. 30, 2225\u20132235 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201600278","type":"journal-article","created":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T23:03:09Z","timestamp":1456959789000},"page":"2225-2235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["CD13\/aminopeptidase N is a negative regulator of mast cell activation"],"prefix":"10.1096","volume":"30","author":[{"given":"Julia S.","family":"Zotz","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Immunology, University Hospital, Rheinisch\u2010Westf\u00e4lische Technische Hochschule (RWTH) Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"W\u00f6lbing","sequence":"additional","affiliation":[{"name":"Department of Dermatology Technical University of Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Lassnig","sequence":"additional","affiliation":[{"name":"Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies","family":"Kauffmann","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Immunology, University Hospital, Rheinisch\u2010Westf\u00e4lische Technische Hochschule (RWTH) Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Schulte","sequence":"additional","affiliation":[{"name":"Institute of Physiology II, University of Freiburg Freiburg Germany"},{"name":"Centre 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