| First Author | Hu W | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 4 | Pages | 109545 |
| PubMed ID | 38617557 | Mgi Jnum | J:352342 |
| Mgi Id | MGI:7625081 | Doi | 10.1016/j.isci.2024.109545 |
| Citation | Hu W, et al. (2024) Spatiotemporal orchestration of macrophage activation trajectories by Vgamma4 T cells during skin wound healing. iScience 27(4):109545 |
| abstractText | Dysregulated macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes underlies impaired cutaneous wound healing. This study reveals Vgamma4(+) gammadelta T cells spatiotemporally calibrate macrophage trajectories during skin repair via sophisticated interferon-gamma (IFN-gamma) conditioning across multiple interconnected tissues. Locally within wound beds, infiltrating Vgamma4(+) gammadelta T cells directly potentiate M1 activation and suppress M2 polarization thereby prolonging local inflammation. In draining lymph nodes, infiltrated Vgamma4(+) gammadelta T cells expand populations of IFN-gamma-competent lymphocytes which disseminate systemically and infiltrate into wound tissues, further enforcing M1 macrophages programming. Moreover, Vgamma4(+)gammadelta T cells flushed into bone marrow stimulate increased IFN-gamma 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 Vgamma4(+) gammadelta T cells provides a sophisticated immunological mechanism regulating inflammation timing and resolution during skin repair. |
