Development of image analysis tool to evaluate Langerhans cell migration after exposure to isothiazolinones.

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2025-03-13 DOI:10.1007/s00204-025-04013-3
Christelle Oltramare, Olivier Burri, Nancy B Hopf, Sandra Jaccoud, Arne Seitz, Lee Ann Applegate, Nathalie Hirt-Burri, Aurélie Berthet
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Abstract

Incidence of allergic contact dermatitis (ACD) is rising worldwide as a consequence of raising chemical exposure, especially from biocides present in common water-based products such as cosmetics and household products. Understanding the biological processes involved in skin sensitization is crucial to mitigating ACD. Migration of Langerhans cells to the basal lamina of the skin is a key step in sensitization. Animal testing for sensitization has been largely replaced by alternative in vitro methods due to ethical concerns. This study presents an open-source program using QuPath software enhanced with machine learning to analyze Langerhans cells migration in immunostained human skin samples. We validated scripts for automated detection of skin layers and Langerhans cells position, enabling accurate, reproducible analysis. An ex vivo human skin organo-culture model was used to test Langerhans cells migration after 24-h exposure to four different isothiazolinones diluted in water at different concentrations. The initial results show that the water vehicle has an impact on Langerhans cells migration. We also observed a different Langerhans cells migration pattern for methylisothiazolinone and benzothiazolinone exposed skin compared to octylisothiazolinone. The results suggest that only octylisothiazolinone can induce Langerhans cells migration to the basal lamina of the epidermis as described for sensitizers. This automated approach represents a advancement in ACD risk assessment by minimizing the subjectivity and labor involved in Langerhans cells analysis, providing a valuable tool for future research.

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过敏性接触性皮炎(ACD)的发病率在全球范围内呈上升趋势,其原因是接触化学物质的机会越来越多,尤其是化妆品和家用产品等常见水基产品中的杀菌剂。了解皮肤过敏的生物过程对于减轻过敏性接触性皮炎至关重要。朗格汉斯细胞向皮肤基底层迁移是致敏的关键步骤。出于伦理方面的考虑,动物致敏试验在很大程度上已被其他体外方法所取代。本研究利用机器学习增强的 QuPath 软件提出了一个开源程序,用于分析免疫染色人体皮肤样本中朗格汉斯细胞的迁移。我们验证了自动检测皮肤层和朗格汉斯细胞位置的脚本,从而实现了准确、可重复的分析。我们使用了一个体外人体皮肤器官培养模型,来测试朗格汉斯细胞在暴露于四种不同浓度的异噻唑啉酮稀释水 24 小时后的迁移情况。初步结果显示,水载体对朗格汉斯细胞的迁移有影响。我们还观察到,与辛基异噻唑啉酮相比,接触甲基异噻唑啉酮和苯并噻唑啉酮的皮肤的朗格汉斯细胞迁移模式有所不同。结果表明,只有辛基异噻唑啉酮能诱导朗格汉斯细胞向表皮基底层迁移,这与敏化剂的作用相同。这种自动方法最大程度地减少了朗格汉斯细胞分析中的主观性和工作量,为未来的研究提供了一种宝贵的工具,是 ACD 风险评估的一大进步。
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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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