{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T15:26:09Z","timestamp":1784388369009,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T00:00:00Z","timestamp":1490918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002722","name":"AllerGen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002722","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Haemopoietic progenitor cells (<jats:styled-content style=\"fixed-case\">HPC<\/jats:styled-content>) migrate to sites of allergic inflammation where, upon stimulation with epithelial cytokines, they produce Th2 cytokines and differentiate into mature eosinophils and basophils. They also express Toll\u2010like receptors (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>) involved in antimicrobial responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study was to compare <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> expression on peripheral blood <jats:styled-content style=\"fixed-case\">HPC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u2010induced responses, in particular changes in epithelial cytokine receptors, in healthy and asthmatic subjects at baseline and following allergen challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ten healthy and 11 allergic asthmatic subjects were studied. <jats:styled-content style=\"fixed-case\">HPC<\/jats:styled-content>\u2010enriched cell populations were stimulated with <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20102, <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20104 or <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20109 ligands. <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> expression by circulating <jats:styled-content style=\"fixed-case\">HPC<\/jats:styled-content> and interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u201025 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017<jats:styled-content style=\"fixed-case\">RB<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201033 (<jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content>2) and thymic stromal lymphopoietin receptor (<jats:styled-content style=\"fixed-case\">TSLPR<\/jats:styled-content>) expression after <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> ligation were examined by flow cytometry at baseline and, in asthmatics, following allergen challenge. The effects of dexamethasone (Dex) on <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u2010induced responses were also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Asthmatics had significantly lower circulating <jats:styled-content style=\"fixed-case\">HPC<\/jats:styled-content> expressing <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20102 and <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20109 with a similar trend for <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20104. <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20104 stimulation of <jats:styled-content style=\"fixed-case\">HPC<\/jats:styled-content> yielded higher numbers of <jats:styled-content style=\"fixed-case\">TSLPR<\/jats:styled-content>+ cells in asthmatics compared with healthy subjects. A similar trend was seen for <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20109 ligation, an effect further augmented by allergen inhalation. Allergen challenge also enhanced <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content>2 expression on <jats:styled-content style=\"fixed-case\">HPC<\/jats:styled-content>. Treatment with Dex in vitro increased <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20104\u2010induced <jats:styled-content style=\"fixed-case\">TSLPR<\/jats:styled-content> expression but had no effect on other epithelial cytokine receptors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>These data demonstrate an interaction between allergen and <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> ligand exposure in asthmatics. Allergen inhalation augments the <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u2010induced inflammatory response by <jats:styled-content style=\"fixed-case\">HPC<\/jats:styled-content>, possibly leading to increased \u201cin situ haemopoiesis\u201d through up\u2010regulation of <jats:styled-content style=\"fixed-case\">TSLPR<\/jats:styled-content>. These findings show that <jats:styled-content style=\"fixed-case\">HPC<\/jats:styled-content> may be a part of the pro\u2010inflammatory cascade in pathogen\u2010induced asthma exacerbation through their increased responsiveness to <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> stimulation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12913","type":"journal-article","created":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T10:42:43Z","timestamp":1488364963000},"page":"900-908","source":"Crossref","is-referenced-by-count":11,"title":["Toll\u2010like receptor\u2010induced expression of epithelial cytokine receptors on haemopoietic progenitors is altered in allergic asthma"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9862-6703","authenticated-orcid":false,"given":"D.","family":"Tworek","sequence":"first","affiliation":[{"name":"Department of Medicine McMaster University Hamilton ON Canada"},{"name":"Department of Internal Diseases, Asthma and Allergy Medical University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Heroux","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. N.","family":"O'Byrne","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. M.","family":"O'Byrne","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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