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One potential pathomechanism is senescence, which causes permanent growth arrest with a pro-inflammatory environment and may be associated with a chronic wound healing disorder. SM is known to induce chronic senescence in human mesenchymal stem cells which are subsequently unable to fulfill their regenerative function in the wound healing process. As dermal fibroblasts are crucial for cutaneous wound healing by being responsible for granulation tissue formation and synthesis of the extracellular matrix, SM exposure might also impair their function in a similar way. This study, therefore, investigated the SM sensitivity of primary human dermal fibroblasts (HDF) by determining the dose\u2013response curve. Non-lethal concentrations LC<jats:sub>1<\/jats:sub> (3\u00a0\u00b5M) to LC<jats:sub>25<\/jats:sub> (65\u00a0\u00b5M) were used to examine the induction of senescence. HDF were exposed once to 3\u00a0\u00b5M, 13\u00a0\u00b5M, 24\u00a0\u00b5M, 40\u00a0\u00b5M or 65\u00a0\u03bcM SM, and were then cultured for 31\u00a0days. Changes in morphology as well as at the genetic and protein level were investigated. For the first time, HDF were shown to undergo senescence in a time- and concentration-dependent manner after SM exposure. They developed a characteristic senescence phenotype and expressed various senescence markers. Proinflammatory cytokines and chemokines were significantly altered in SM-exposed HDF as part of a senescence-associated secretory phenotype. The senescent fibroblasts can thus be considered a contributor to the SM-induced chronic wound healing disorder and might serve as a new therapeutic target in the future.<\/jats:p>","DOI":"10.1007\/s00204-022-03346-7","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T17:25:52Z","timestamp":1659115552000},"page":"3053-3066","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Sulfur mustard single-dose exposure triggers senescence in primary human dermal fibroblasts"],"prefix":"10.1007","volume":"96","author":[{"given":"Gabriele","family":"Horn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Sch\u00e4fers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Thiermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"V\u00f6lkl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2041-0034","authenticated-orcid":false,"given":"Simone","family":"Rothmiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"issue":"12","key":"3346_CR1","doi-asserted-by":"publisher","first-page":"5820","DOI":"10.1093\/rheumatology\/keab168","volume":"60","author":"E Adami","year":"2021","unstructured":"Adami E, Viswanathan S, Widjaja AA, Ng B, Chothani S, Zhihao N et al (2021) IL11 is elevated in systemic sclerosis and IL11-dependent ERK signalling underlies TGF\u03b2-mediated activation of dermal fibroblasts. 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