<p>The excessive accumulation of neutrophils within the epidermis is a significant hallmark of cutaneous diseases; however, the mechanisms governing neutrophil transepidermal migration (NTEM) remain inadequately understood. In this study, we develop trichromatic-fluorescence-labeled chimeric mice by utilizing <i>Cx3cr1</i><sup>GFP/+</sup><i>Lyz2</i><sup>RFP/+</sup> mice as bone marrow donors and Krt14<sup>YFP/+</sup> mice as recipients. This approach enables us to visualize the process of NTEM and the crosstalk between neutrophils and monocytes in a murine model of irritant contact dermatitis (ICD). Intravital imaging reveals a preferential transmigration of neutrophils through hair follicle (HF), where dermal neutrophils exhibit limited mobility and interact with dermal monocytes. Notably, 18 h following hapten exposure, dermal neutrophils continuously migrate toward HF regions and form clusters within 3 h. Importantly, MMP-9 is identified as essential for the NTEM process; the depletion of dermal monocytes results in a significant reduction of MMP-9 expression in the skin and inhibits the NTEM process in ICD. Mechanistically, dermal monocytes are found to be a crucial source of the cytokines TNF-α and CXCL2, which promote the upregulation of MMP-9 in neutrophils. Therefore, our results highlight HF regions as crucial gateways for dermal monocyte-modulated NTEM and provide visual insights into the crosstalk between neutrophils and monocytes in inflammatory skin disorders.</p><p></p>

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The crosstalk of monocyte-neutrophil in hair follicles regulates neutrophil transepidermal migration in contact dermatitis

  • Zhan Fan,
  • Yilun Xu,
  • Yafang Lu,
  • Xinlin Li,
  • Mengli Xu,
  • Jinxin Liu,
  • Zhenzhen Cai,
  • Jiayang Liu,
  • Jingping Su,
  • Jialu Wang,
  • Qingming Luo,
  • Zhihong Zhang,
  • Zheng Liu

摘要

The excessive accumulation of neutrophils within the epidermis is a significant hallmark of cutaneous diseases; however, the mechanisms governing neutrophil transepidermal migration (NTEM) remain inadequately understood. In this study, we develop trichromatic-fluorescence-labeled chimeric mice by utilizing Cx3cr1GFP/+Lyz2RFP/+ mice as bone marrow donors and Krt14YFP/+ mice as recipients. This approach enables us to visualize the process of NTEM and the crosstalk between neutrophils and monocytes in a murine model of irritant contact dermatitis (ICD). Intravital imaging reveals a preferential transmigration of neutrophils through hair follicle (HF), where dermal neutrophils exhibit limited mobility and interact with dermal monocytes. Notably, 18 h following hapten exposure, dermal neutrophils continuously migrate toward HF regions and form clusters within 3 h. Importantly, MMP-9 is identified as essential for the NTEM process; the depletion of dermal monocytes results in a significant reduction of MMP-9 expression in the skin and inhibits the NTEM process in ICD. Mechanistically, dermal monocytes are found to be a crucial source of the cytokines TNF-α and CXCL2, which promote the upregulation of MMP-9 in neutrophils. Therefore, our results highlight HF regions as crucial gateways for dermal monocyte-modulated NTEM and provide visual insights into the crosstalk between neutrophils and monocytes in inflammatory skin disorders.