{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T02:29:52Z","timestamp":1759026592014,"version":"3.37.3"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,4,16]],"date-time":"2015-04-16T00:00:00Z","timestamp":1429142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001736","name":"German-Israeli Foundation for Scientific Research and Development","doi-asserted-by":"crossref","award":["993\/2008"],"award-info":[{"award-number":["993\/2008"]}],"id":[{"id":"10.13039\/501100001736","id-type":"DOI","asserted-by":"crossref"}]},{"name":"German Research Council","award":["DFG; HA 2393\/6-1","CRC\/SFB832","project A14"],"award-info":[{"award-number":["DFG; HA 2393\/6-1","CRC\/SFB832","project A14"]}]},{"DOI":"10.13039\/100008672","name":"Wilhelm Sander Foundation","doi-asserted-by":"crossref","award":["1999.049.2"],"award-info":[{"award-number":["1999.049.2"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Inserm and le Label de La Ligue contre le Cancer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2015,7]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Mastocytosis is characterized by the accumulation of mast cells (MC<\/jats:styled-content>s) associated with activating mutations of KIT<\/jats:styled-content><\/jats:italic>. Tumor necrosis factor\u2010related apoptosis\u2010inducing ligand receptors (TRAIL<\/jats:styled-content>\u2010Rs) are preferentially expressed on neoplastic cells and induce the extrinsic apoptotic pathway. Recent studies reported on the expression of TRAIL<\/jats:styled-content>\u2010Rs and TRAIL<\/jats:styled-content>\u2010induced apoptosis in cultured human MC<\/jats:styled-content>s, which depend on stem cell factor (SCF<\/jats:styled-content>)\u2010induced or constitutive KIT<\/jats:styled-content> activation.<\/jats:p><\/jats:sec>Material and methods<\/jats:title>We sought to further define the impact of TRAIL<\/jats:styled-content>\u2010Rs on MC<\/jats:styled-content>s in vivo<\/jats:italic> and in vitro<\/jats:italic>. Using Cre\/loxP recombination, we generated mice with MC<\/jats:styled-content>\u2010specific and ubiquitous knockout of TRAIL<\/jats:styled-content>\u2010R. In these mice, anaphylaxis and numbers of MC<\/jats:styled-content>s were investigated. We also explored the expression and function of TRAIL<\/jats:styled-content>\u2010Rs in cultured murine and human MC<\/jats:styled-content>s upon activation of KIT<\/jats:styled-content>. By conducting immunofluorescence staining, we analyzed the expression of TRAIL<\/jats:styled-content>\u2010Rs in MC<\/jats:styled-content>s infiltrating the bone marrow of patients with mastocytosis.<\/jats:p><\/jats:sec>Results<\/jats:title>MC<\/jats:styled-content>\u2010specific deletion of TRAIL<\/jats:styled-content>\u2010R was associated with a slight, but significant increase in anaphylaxis. Numbers of MC<\/jats:styled-content>s in MC<\/jats:styled-content>\u2010specific knockouts of TRAIL<\/jats:styled-content>\u2010R were comparable to controls. Whereas cultured IL<\/jats:styled-content>\u20103\u2010dependent murine MC<\/jats:styled-content>s from wild\u2010type mice were resistant to TRAIL<\/jats:styled-content>\u2010induced apoptosis, SCF<\/jats:styled-content>\u2010stimulated MC<\/jats:styled-content>s underwent apoptosis in response to TRAIL<\/jats:styled-content>. Interestingly, activating KIT<\/jats:styled-content><\/jats:italic> mutations also promoted sensitivity to TRAIL<\/jats:styled-content>\u2010mediated apoptosis in human MC<\/jats:styled-content>s. In line with these findings, MC<\/jats:styled-content>s infiltrating the bone marrow of patients with mastocytosis expressed TRAIL<\/jats:styled-content>\u2010R1.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Activation of KIT<\/jats:styled-content> regulates the function of TRAIL<\/jats:styled-content>\u2010Rs in MC<\/jats:styled-content>s. TRAIL<\/jats:styled-content>\u2010R1 may represent an attractive diagnostic and therapeutic target in diseases associated with KIT<\/jats:styled-content><\/jats:italic> mutations, such as mastocytosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.12612","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T18:53:33Z","timestamp":1427914413000},"page":"764-774","source":"Crossref","is-referenced-by-count":5,"title":["Activation of KIT<\/scp> modulates the function of tumor necrosis factor\u2010related apoptosis\u2010inducing ligand receptor (TRAIL\u2010R) in mast cells"],"prefix":"10.1111","volume":"70","author":[{"given":"A.","family":"F\u00f6rster","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. P.","family":"Grotha","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. M.","family":"Seeger","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Hygiene and Center for Molecular Medicine (CMMC) University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Rabenhorst","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Gehring","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy Hannover Medical School Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U.","family":"Raap","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy Hannover Medical School Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"L\u00e9tard","sequence":"additional","affiliation":[{"name":"Inserm, U1068, CRCM, (Signaling, Hematopoiesis and Mechanism of Oncogenesis) Institut Paoli\u2010Calmettes, Aix\u2010Marseille University Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Dubreuil","sequence":"additional","affiliation":[{"name":"Inserm, U1068, CRCM, (Signaling, Hematopoiesis and Mechanism of Oncogenesis) Institut Paoli\u2010Calmettes, Aix\u2010Marseille University Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Kashkar","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Hygiene and Center for Molecular Medicine (CMMC) University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Walczak","sequence":"additional","affiliation":[{"name":"Centre for Cell Death, Cancer and Inflammation (CCCI) UCL Cancer Institute University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Roers","sequence":"additional","affiliation":[{"name":"Medical Faculty Carl Gustav Carus Institute for Immunology University of Technology Dresden Dresden Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,4,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3427"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.07.007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2755"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2011.10.007"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.07.003"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(01)00038-8"},{"key":"e_1_2_10_8_1","first-page":"291","volume-title":"World Health Organization (WHO) Classification of Tumours Pathology and Genetics of Tumours of the Haematopoietic and Lymphoid Tissues","author":"Valent P","year":"2001"},{"key":"e_1_2_10_9_1","first-page":"54","volume-title":"World Health Organization Classification of Tumours. 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