{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:48:42Z","timestamp":1788202122930,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T00:00:00Z","timestamp":1551139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Siglec\u20107 is an inhibitory receptor (<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>) expressed on human blood eosinophils. Whereas activation of other <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>s, including Siglec\u20108 and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>300a, has been shown to downregulate eosinophil function, little is known about the role of Siglec\u20107 on human eosinophils.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine Siglec\u20107 expression and function in eosinophils from normal (<jats:styled-content style=\"fixed-case\">ND<\/jats:styled-content>) and eosinophilic (<jats:styled-content style=\"fixed-case\">EO<\/jats:styled-content>) donors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eosinophil expression of Siglec\u20107 was quantified by flow cytometry and quantitative <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. Soluble Siglec\u20107 (sSiglec\u20107) levels were measured by <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content> in serum. The effect of Siglec\u20107 on eosinophil viability and degranulation was assessed in\u00a0vitro by AnnexinV\u2010<jats:styled-content style=\"fixed-case\">FITC<\/jats:styled-content>\/7\u2010<jats:styled-content style=\"fixed-case\">AAD<\/jats:styled-content> staining and by measuring <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>\u2010induced mediator release in culture supernatants. Signal transduction was studied by Western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Siglec\u20107 was expressed ex\u00a0vivo on blood eosinophils from all eosinophilic and normal individuals studied. Siglec\u20107 surface, but not <jats:italic><jats:styled-content style=\"fixed-case\">SIGLEC<\/jats:styled-content>\u20107<\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression, was correlated with absolute eosinophil count (<jats:styled-content style=\"fixed-case\">AEC<\/jats:styled-content>). Siglec\u20107 was upregulated on purified eosinophils after in\u00a0vitro stimulation with <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105. Serum sSiglec\u20107 was detectable in 133\/144 subjects tested and correlated with <jats:styled-content style=\"fixed-case\">AEC<\/jats:styled-content>. Siglec\u20107 cross\u2010linking inhibited <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>\u2010induced release of eosinophil peroxidase, <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1, and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 (n\u00a0=\u00a07\u20138) but did not promote eosinophil apoptosis (n\u00a0=\u00a05). Finally, Siglec\u20107 cross\u2010linking on <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>\u2010activated eosinophils induced phosphorylation of <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>\u20101 and de\u2010phosphorylation of <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 and p38.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Siglec\u20107 is constitutively expressed on human eosinophils and downmodulates eosinophil activation. Targeting of Siglec\u20107 on eosinophils might enhance treatment efficacy in eosinophil\u2010driven disorders. Conversely, therapeutic interventions that inhibit Siglec\u20107 could have unanticipated consequences and promote eosinophilic inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13730","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T03:39:11Z","timestamp":1548733151000},"page":"1257-1265","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Siglec\u20107 on peripheral blood eosinophils: Surface expression and function"],"prefix":"10.1111","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9373-7789","authenticated-orcid":false,"given":"Fanny","family":"Legrand","sequence":"first","affiliation":[{"name":"Human Eosinophil Section Laboratory of Parasitic Diseases National Institute of Allergy and Infectious Diseases Bethesda 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