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Understanding and mimicking compromised skin is essential to further develop appropriate therapeutic solutions. This study aimed to develop new <jats:italic>in vitro<\/jats:italic> 3D models mimicking acneic skin, by combining two main factors involved in the physiopathology, namely, altered sebum composition and <jats:italic>C.\u00a0acnes<\/jats:italic> invasion. Normal human keratinocytes were first used to generate reconstructed human epidermis (RHE) that were then left untreated (control) or treated topically with a combination of both peroxidized squalene and <jats:italic>C.\u00a0acnes<\/jats:italic> cultures. Once validated, this model considered relevant to mimic acneic skin, was further improved by using different phylotypes of <jats:italic>C.\u00a0acnes<\/jats:italic> strains specifically isolated from healthy and acneic patients. While both phylotypes IB and II did not significantly alter RHE, <jats:italic>C.\u00a0acnes<\/jats:italic> IA1 strains induce major acneic skin hallmarks such as hyperkeratinization, secreted inflammation and altered barrier function. Interestingly, these results are obtained independently of the origin of IA1 phylotypes (acneic vs. healthy patient), thus suggesting a role of the ecosystem in controlling <jats:italic>C.\u00a0acnes<\/jats:italic> virulence in healthy skin. In conclusion, by combining two major factors involved in the physiopathology of acne, we (1) succeeded to design <jats:italic>in vitro<\/jats:italic> 3D models mimicking this skin disorder and (2) highlighted how <jats:italic>C.\u00a0acnes<\/jats:italic> phylotypes can have an impact on epidermal physiology. These relevant models will be suitable for the substantiation of therapeutic molecules dedicated to acne treatment.<\/jats:p>","DOI":"10.1111\/exd.14268","type":"journal-article","created":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T10:43:43Z","timestamp":1608806623000},"page":"347-357","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Development and characterization of a 3D <i>in vitro<\/i> model mimicking acneic skin"],"prefix":"10.1111","volume":"30","author":[{"given":"Marine","family":"Laclaverie","sequence":"first","affiliation":[{"name":"R&amp;D Department SILAB Brive CEDEX France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-7077","authenticated-orcid":false,"given":"Pauline","family":"Rouaud\u2010Tinguely","sequence":"additional","affiliation":[{"name":"R&amp;D Department SILAB Brive CEDEX 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