Spatiotemporal orchestration of macrophage activation trajectories by Vγ4 T cells during skin wound healing

• Published in: iScience 2024-04, Vol.27 (4), p.109545-109545, Article 109545
• Main Authors: Hu, Wengang, Zhang, Xiaorong, Liu, Zhongyang, Yang, Jiacai, Sheng, Hao, Liu, Zhihui, Chen, Cheng, Shang, Ruoyu, Chen, Yunxia, Lu, Yifei, Hu, Xiaohong, Huang, Yong, Yin, Wenjing, Cai, Xin, Fan, Dejiang, Yan, Lingfeng, Hao, Jianlei, Luo, Gaoxing, He, Weifeng
• Format: Article
• Language: English
• Subjects: Biological sciences; Components of the immune system; Immune response
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.109545

Dysregulated macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes underlies impaired cutaneous wound healing. This study reveals Vγ4+ γδ T cells spatiotemporally calibrate macrophage trajectories during skin repair via sophisticated interferon-γ (IFN-γ) conditioning across multiple interconnected tissues. Locally within wound beds, infiltrating Vγ4+ γδ T cells directly potentiate M1 activation and suppress M2 polarization thereby prolonging local inflammation. In draining lymph nodes, infiltrated Vγ4+ γδ T cells expand populations of IFN-γ-competent lymphocytes which disseminate systemically and infiltrate into wound tissues, further enforcing M1 macrophages programming. Moreover, Vγ4+γδ T cells flushed into bone marrow stimulate increased IFN-γ production, which elevates the output of pro-inflammatory Ly6C+monocytes. Mobilization of these monocytes continually replenishes the M1 macrophage pool in wounds, preventing phenotypic conversion to M2 activation. Thus, multi-axis coordination of macrophage activation trajectories by trafficking Vγ4+ γδ T cells provides a sophisticated immunological mechanism regulating inflammation timing and resolution during skin repair. [Display omitted] •Vγ4+γδ T cells prolong inflammation via sustained M1 activation and M2 suppression•Local Vγ4+γδ T cells in wounds mainly modulate macrophages polarization via IFN-γ•IFN-γ+ lymphocytes promoted by infiltrating Vγ4+γδ T cells enforce M1 programming•Infiltrated Vγ4+ γδ T cells in bone marrow increases Ly6C+ monocytes generation Biological sciences; Immune response; Components of the immune system