AbstractLangerhans cells (LCs) are resident dendritic cells in the epidermis and their roles in presenting antigens derived from microorganisms present in the skin has been well appreciated. However, it is generally thought that incoming neutrophils are mainly responsible for eradicating invading pathogens in the early stage of wounds and a role of LCs in innate immunity is elusive.

摘要朗格汉斯细胞（LC）是表皮中的常驻树突状细胞，它们在呈递来自皮肤中存在的微生物的抗原中的作用已被充分认识。然而，人们普遍认为，进入的中性粒细胞主要负责在伤口早期根除入侵的病原体，而LC在先天免疫中的作用是难以捉摸的。

In the current study, we showed that wounds absent of LCs had a delayed closure. Mechanistically, LCs were the primary cells in warding off bacteria invasion at the early stage of wound healing. Without LCs, commensal bacteria quickly invaded and propagated in the wounded area. keratinocytes surrounding the wounds responded to the excessive bacteria by elevated production of CXCL5, resulting in an over-influx of neutrophils.

。从机制上讲，LC是在伤口愈合早期抵御细菌侵袭的原代细胞。没有LCs，共生细菌会迅速入侵并在受伤区域繁殖。伤口周围的角质形成细胞通过CXCL5的产生增加对过量细菌作出反应，导致中性粒细胞过度流入。

The over-presence of activated neutrophils, possibly together with the aggravated invasion of bacteria, was detrimental to epidermal progenitor cell propagation and re-epithelialization. These observations underscore an indispensable role of LCs as effective guardians that preclude both bacteria invasion and damages inflicted by secondary inflammation.Highlights.

活化的中性粒细胞的过度存在，可能与细菌的侵袭加剧一起，对表皮祖细胞的增殖和再上皮化有害。这些观察结果强调了LC作为有效监护人的不可或缺的作用，可以防止细菌入侵和继发性炎症造成的损害。亮点。

Langerhans cells (LCs) are considered resident dendritic cells in the epidermis and their roles in presenting antigens derived from microorganisms present in the skin has been well appreciated.

朗格汉斯细胞（LC）被认为是表皮中的常驻树突状细胞，它们在呈递来自皮肤中存在的微生物的抗原中的作用已被充分认识。

However, the role of LCs in wound healing is controversial.

然而，LC在伤口愈合中的作用是有争议的。

In this study, we demonstrate that wounds absent of LCs had a delayed closure.

在这项研究中，我们证明了LCs缺失的伤口延迟闭合。

Mechanistically, LCs may be the primary cells in warding off bacteria invasion at the early stage of wound healing.

从机制上讲，LC可能是在伤口愈合早期抵御细菌侵袭的原代细胞。

Without LCs, propagation of commensal bacteria was evident in the early stage of wounds, which stimulated keratinocytes to overproduce CXCL5, a neutrophil chemokine. Over-influx of 3neutrophils significantly slowed epidermal progenitor cell propagation, re-epithelization and wound healing in the absence of LCs..

没有LC，共生细菌的繁殖在伤口的早期阶段很明显，这刺激了角质形成细胞过度产生中性粒细胞趋化因子CXCL5。在没有LC的情况下，过度流入的3种中性粒细胞显着减缓了表皮祖细胞的增殖，再上皮化和伤口愈合。。

IntroductionEpithelium is a tissue featured for its direct exposure to the external environment and the associated various commensal and pathogenic microorganisms and noxious agents [1]. In terms of skin, it is the largest organ of human body and forms a protective shield against microbial invasion and a variety of environmental inflictions [1].

引言上皮是一种直接暴露于外部环境以及相关的各种共生和致病微生物和有毒物质的组织。就皮肤而言，它是人体最大的器官，对微生物入侵和各种环境造成的影响形成保护屏障（1）。

As such, epidermis, the skin epithelium, has a relatively fast turnover rate owing to continuous wear and tear. Stem and progenitor cells residing in the bottom layer of skin epithelium actively replace the terminally differentiated but wearing keratinocytes on top of them [2]. During wounding, skin re-epithelization also involves collective migration of keratinocytes across the injured dermis [3].Formation of a proper epithelial barrier after acute injury requires a coordinated action and cross-talk of keratinocytes and immune cells at the wound site.

因此，由于持续的磨损，表皮（皮肤上皮）具有相对较快的周转率。位于皮肤上皮底层的干细胞和祖细胞主动替代终末分化但在其顶部磨损的角质形成细胞（2）。在受伤期间，皮肤再上皮化还涉及角质形成细胞在受损真皮上的集体迁移（3）。急性损伤后形成适当的上皮屏障需要伤口部位角质形成细胞和免疫细胞的协调作用和相互作用。

For example, impacts of neutrophils in wound healing can be viewed as a double-edged sword [4]. Too few neutrophils risks infection and delayed epithelium recovery [5], whereas over-persistence of neutrophils in injured tissues also delays epithelium healing through collateral tissue damage by inflammatory effectors [6].

例如，中性粒细胞在伤口愈合中的影响可以被视为一把双刃剑（4）。中性粒细胞过少会导致感染和上皮恢复延迟（5），而中性粒细胞在受损组织中的过度持续也会通过炎症效应物的附带组织损伤延迟上皮愈合（6）。

Therefore, neutrophil recruitment and activation in wounding site is tightly tailored, a regulation process has not been clearly addressed. Langerhans cells (LCs) inhabit the epidermis and account for a majority of immune cells in the skin epidermis in resting state. The localization of LCs suggests that these immune cells will be one of the first immune cell types to interact with substances and infectious agents invading the skin, especially in case of wounding.

因此，伤口部位的中性粒细胞募集和激活是严格定制的，调节过程尚未明确解决。朗格汉斯细胞（LC）栖息在表皮中，占静息状态下皮肤表皮中免疫细胞的大部分。LC的定位表明，这些免疫细胞将是首批与入侵皮肤的物质和感染因子相互作用的免疫细胞类型之一，尤其是在受伤的情况下。

On the other hand, keratinocytes which are the epithelial cells in the skin must also sense and respo.

另一方面，作为皮肤上皮细胞的角质形成细胞也必须感知和响应。

Data availability

数据可用性

All data and materials generated in this study are available from the corresponding author upon reasonable request.

本研究中产生的所有数据和材料均可根据合理要求从通讯作者处获得。

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Mi QS, Xu YP, Wang H, Qi RQ, Dong Z, Zhou L. Deletion of microRNA miR-223 increases Langerhans cell cross-presentation. Int J Biochem Cell Biol. 2013;45:395–400.Article

Mi QS，Xu YP，Wang H，Qi RQ，Dong Z，Zhou L.microRNA miR-223的缺失增加了朗格汉斯细胞的交叉呈递。Int J生物化学细胞生物学。2013年；45:395–400.文章

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Download referencesAcknowledgementsWe thank Junli Xuan, Shuangshuang Liu, Qiong Huang and Jingyao Chen from the Core Facilities, Zhejiang University School of Medicine for the technical support. In addition, we thank Qin Han for her technical assistance on Two-photon Microscopy. This work was supported by grants from the National Natural Science Foundation of China (82172206 to W-Q.T.

下载参考文献致谢我们感谢浙江大学医学院核心设施的JunliXuan，Shuangshuang Liu，Qiong Huang和Jingyao Chen提供的技术支持。此外，我们感谢秦汉在双光子显微镜方面的技术援助。这项工作得到了国家自然科学基金（82172206至W-Q.T.）的资助。

and 32170894 to X.Z.S.) and the Natural Science Foundation of Zhejiang Province (LZ22C080001 to X.Z.S).Author informationAuthors and AffiliationsDepartment of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZheng-Cai Wang, Yan-Yan Hu & Wei-Qiang TanDepartment of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaXiao Z.

和32170894至X.Z.S.）和浙江省自然科学基金（LZ22C080001至X.Z.S）。作者信息作者和附属机构浙江大学医学院邵逸夫爵士医院整形外科，杭州，中国浙江省杭州市浙江大学医学院第二附属医院生理学系和心脏病学系，浙江省杭州市肖Z。

ShenAuthorsZheng-Cai WangView author publicationsYou can also search for this author in.

ShenAuthorsZheng Cai WangView作者出版物您也可以在中搜索此作者。

PubMed Google ScholarYan-Yan HuView author publicationsYou can also search for this author in

PubMed Google ScholarYan Yan HuView作者出版物您也可以在

PubMed Google ScholarXiao Z. ShenView author publicationsYou can also search for this author in

PubMed Google ScholarXiao Z.ShenView作者出版物您也可以在

PubMed Google ScholarWei-Qiang TanView author publicationsYou can also search for this author in

PubMed谷歌学者Wei Qiang TanView作者出版物您也可以在

PubMed Google ScholarContributionsConceptualization of the study: XZS and ZCW. Designed the experiments: XZS, ZCW and WQT. Supervised the study: XZS and WQT. All experiments: ZCW. Facilitating in animal models: YYH. Statistical analyses: ZCW. Wrote and revised the paper: XZS and ZCW.Corresponding authorsCorrespondence to.

PubMed谷歌学术贡献研究概念：XZS和ZCW。设计了实验：XZS，ZCW和WQT。监督研究：XZS和WQT。所有实验：ZCW。在动物模型中促进：YYH。统计分析：ZCW。撰写并修订了论文：XZS和ZCW。通讯作者通讯。

Xiao Z. Shen or Wei-Qiang Tan.Ethics declarations

沈晓子或谭伟强。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Ethics approval and consent to participate

道德批准和同意参与

This study was approved by the Ethical Review Committee of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. All methods in this research were performed in accordance with the relevant guidelines and regulations. All animal experiments were approved by the Institutional Animal Care and Use Committee at Zhejiang University (approval number: ZJU20210274)..

这项研究得到了浙江大学医学院邵逸夫爵士医院伦理审查委员会的批准。本研究中的所有方法均按照相关指南和规定进行。所有动物实验均经浙江大学机构动物护理和使用委员会批准（批准号：ZJU20210274）。。

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Reprints and permissionsAbout this articleCite this articleWang, ZC., Hu, YY., Shen, X.Z. et al. Absence of Langerhans cells resulted in over-influx of neutrophils and increased bacterial burden in skin wounds.

转载和许可本文引用本文Wang，ZC。，胡，YY。，Shen，X.Z.等人。朗格汉斯细胞的缺乏导致中性粒细胞的过度流入和皮肤伤口细菌负荷的增加。

Cell Death Dis 15, 760 (2024). https://doi.org/10.1038/s41419-024-07143-1Download citationReceived: 05 February 2024Revised: 02 October 2024Accepted: 08 October 2024Published: 19 October 2024DOI: https://doi.org/10.1038/s41419-024-07143-1Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

细胞死亡Dis 15760（2024）。https://doi.org/10.1038/s41419-024-07143-1Download引文收到日期：2024年2月5日修订日期：2024年10月2日接受日期：2024年10月8日发布日期：2024年10月19日OI：https://doi.org/10.1038/s41419-024-07143-1Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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