{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T02:02:10Z","timestamp":1781316130552,"version":"3.54.1"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:p>\n                    Topical imiquimod (IMQ), a Toll\u2010like receptor (TLR) 7 agonist, induces transient cutaneous inflammation and is widely used in preclinical research as a \u2018psoriasis\u2010like\u2019 mouse model. However, accumulating evidence indicates substantial divergence between IMQ\u2010driven biology and human plaque psoriasis pathogenesis. To bridge this translational gap, we compare here the experimental conduct, readouts and mechanistic insights engaged by IMQ challenge in mice\n                    <jats:italic>vs<\/jats:italic>\n                    . healthy human participants. Importantly, molecular and cellular analyses indicate that IMQ predominantly activates interferon regulatory factor (IRF) signalling in humans, rather than NF\u2010\u03baB pathways as observed in animals. Moreover, differences in neutrophil response and complement activation were also identified. These discrepancies may reflect interspecies variation in TLR7 expression as well as methodological differences between the animal and human IMQ model. Despite certain limitations related to psoriasis translatability, the human IMQ model has demonstrated translational relevance in several early phase clinical trials. It represents a valuable tool for evaluating target engagement and characterizing downstream pharmacodynamic effects of novel compounds, particularly those targeting the TLR7\u2013IRF\u2010type I interferon axis. In conclusion, the human IMQ model can serve as valuable mechanistic model driving disease\u2010related pathways, rather than as a proxy for plaque psoriasis disease biology. Fit\u2010for\u2010purpose benchmarking and method standardization are essential to maximize translational utility of the IMQ model.\n                  <\/jats:p>","DOI":"10.1002\/bcp.70643","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T01:35:59Z","timestamp":1781314559000},"source":"Crossref","is-referenced-by-count":0,"title":["Lost and found in translation: the value of the human imiquimod model"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1899-6531","authenticated-orcid":false,"given":"Anouk C.","family":"Meijs","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7356-6847","authenticated-orcid":false,"given":"Juliette A.","family":"van den Noort","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Assil","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden Academic Centre for Drug Research Leiden University  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi B.","family":"Klarenbeek","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs","family":"Moerland","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-1609","authenticated-orcid":false,"given":"Tessa","family":"Niemeyer\u2010van der Kolk","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5867-9090","authenticated-orcid":false,"given":"Robert","family":"Rissmann","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden Academic Centre for Drug Research Leiden University  Leiden The Netherlands"},{"name":"Department of Dermatology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.13235"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802999"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2025.09.005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12563"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011\u2010015\u20100795\u2010z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753\u2010024\u201002127\u2010x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.06.019"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12865\u2010021\u201000401\u20103"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b25\u201000060"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.09.021"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2019.07.006"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.04.029"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/immunohorizons.2300003"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2017.1422591"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.11.011"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.05.013"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102003\u201004\u20101078"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1197650"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13771"},{"key":"e_1_2_9_21_1","unstructured":"MeijsAC DeantonioC DreisCet al.The novel first\u2010in\u2010class IL\u20101R3 antagonist SAR445399 reduces skin inflammation in an innovative proof\u2010of\u2010mechanism study with dual immune challenge models and comparator drugs.2025. Abstract no: 1189. Presented at the EADV congress Paris France 17\u201320 September 2025."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.09.214"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X17735756"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13555\u2010025\u201001505\u2010z"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026\u2010024\u201009484\u20107"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1292406"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16180"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70643","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70643","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T01:36:02Z","timestamp":1781314562000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":28,"alternative-id":["10.1002\/bcp.70643"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70643","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]},"article-number":"bcp.70643"}}