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The purpose of this study was to characterize TLR7-mediated inflammation following 7\u00a0days (168\u00a0h) of topical IMQ exposure in healthy volunteers, and to compare the effects of short exposure (48\u00a0h-72\u00a0h) with prolonged exposure (120\u00a0h-168\u00a0h). IMQ (100mg) was applied under occlusion to 5 different tape-stripped treatment sites on the back of 10 healthy participants for a maximum of 7 consecutive days. Erythema and skin perfusion were measured daily up to 168h. Biopsies for immunohistochemical staining and RNA sequencing were collected at 0h, 48h, 72h, 120h and 168h post IMQ application. IMQ triggered an inflammatory response starting at 48h after application, including erythema and perfusion of the skin. At the transcriptomic level, IMQ induced TLR7 signalling, IRF involvement and activation of TNF signalling via NF-\u03baB. Furthermore, an enhanced inflammatory response at the cellular level was observed after prolonged IMQ exposure, with cellular infiltration of dendritic cells, macrophages and T cells which was also corroborated by transcriptomic profiles. No difference was found in the erythema and perfusion response after 168h of IMQ exposure compared to 72h. Prolonged IMQ exposure revealed enhanced cellular responses and additional pathways with modulated activity compared to short exposure and can therefore be of interest as a model for investigational compounds targeting innate and adaptive immune responses.<\/jats:p>","DOI":"10.1007\/s10753-024-02127-x","type":"journal-article","created":{"date-parts":[[2024,8,25]],"date-time":"2024-08-25T23:08:36Z","timestamp":1724627316000},"page":"1366-1377","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Extending the IMQ Model: Deep Characterization of the Human TLR7 Response for Early Drug Development"],"prefix":"10.1007","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7356-6847","authenticated-orcid":false,"given":"Juliette A.","family":"van den Noort","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1120-5100","authenticated-orcid":false,"given":"Salma","family":"Assil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha N.","family":"Ronner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Osse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Pot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yal\u00e7in","family":"Yavuz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Damman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Lubberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Rissmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa Niemeyer-van","family":"der Kolk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Tomljanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon A. 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Approval was granted by the Independent Ethics Committee (Medisch Ethische ToetsingsCommise) of the Foundation \u2018Evaluation of Ethics in Biomedical Research\u2019 (Stichting Beoordeling Ethiek Biomedisch Onderzoek), Assen, The Netherlands (Date 15DEC2021\/NL79321.056.21).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest"}}]}}