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This may be due to limited biomarker response in vitro in cell types that interact as crucial players of in vivo skin sensitisation pathogenesis. Here, we propose a molecular approach to overcome this limitation. In our model, we apply genome editing and blocking of immunoregulatory molecules to increase the range of biomarker modulation by sensitising chemicals. To this end, aryl hydrocarbon receptor (AhR) knockout was done by CRISPR\/Cas9 technology in THP-1 cells and combined with Programmed Cell Death-Ligand (PD-L)1 blockade. AhR-knockout THP-1 in coculture with HaCaT keratinocytes showed increased CD54 expression compared to wild type cells after stimulation with 10\u00a0\u00b5mol\/L dinitrochlorobenzene (DNCB) that was further enhanced by anti-PD-L1. After stimulation of AhR-knockout THP-1 with 200\u00a0\u00b5mol\/L mercaptobenzothiazol or 10\u00a0\u00b5mol\/L DNCB, cocultivated Jurkat T cells significantly increased expression of T cell receptor-associated CD3. No such increase was detected after prior treatment of THP-1 with 150\u00a0\u00b5mol\/L of irritant sodium lauryl sulphate. Additionally, higher levels of inflammatory cytokines MIP-3\u03b1, MIP-1\u03b2, TNF-\u03b1, and IL-8 were found in supernatants of enhanced loose-fit co-culture based sensitisation assay (eLCSA) after substance treatment. Hence, eLCSA allowed to discriminate between sensitisers and non-sensitisers. Thus, inhibition of immunoinhibitory pathway signalling by combining AhR knockout and PD-L1 antibody blockage into an assay involving main acting cell types in skin sensitisation may increase sensitivity and specificity of such assays and allow potency derivation.<\/jats:p>","DOI":"10.1007\/s00204-023-03506-3","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T19:02:06Z","timestamp":1683313326000},"page":"1677-1689","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A new cell line based coculture system for skin sensitisation testing in one single assay using T cells, aryl\u00a0hydrocarbon receptor knockout, and co-inhibitory blockage"],"prefix":"10.1007","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6524-6456","authenticated-orcid":false,"given":"Anna","family":"Sonnenburg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Stahlmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhold","family":"Kreutz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Peiser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"3506_CR1","doi-asserted-by":"publisher","first-page":"2572","DOI":"10.3389\/fimmu.2018.02572","volume":"9","author":"S Ahmad","year":"2018","unstructured":"Ahmad S, Azid NA, Boer JC et al (2018) The key role of TNF-TNFR2 interactions in the modulation of allergic inflammation: a review. 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