T Lymphocytes Attenuate Dermal Scarring by Regulating Inflammation, Neovascularization, and Extracellular Matrix Remodeling

作者：Xinyi Wang, Swathi Balaji, Emily Steen, Hui Li, Meredith Rae, Alexander Blum, Qi Miao, Manish J. Butte, Paul L. Bollyky, Sundeep G. Keswani · 发表于：Advances in Wound Care · 年份：2019 · DOI：10.1089/wound.2019.0981 · 被引用次数：67 · 研究领域：Wound Healing and Treatments、Dermatology and Skin Diseases、Pressure Ulcer Prevention and Management

Objective: While tissue injury and repair are known to involve adaptive immunity, the profile of lymphocytes involved and their contribution to dermal scarring remain unclear. We hypothesized that restoration of T cell deficiency attenuates dermal scarring. Approach: We assessed the temporal–spatial distribution of T lymphocytes and their subtypes during the physiological dermal wound repair process in mice. Also, we compared the scarring outcomes between wild-type (WT) and severe combined immunodeficient (SCID) mice, which are lymphocyte deficient. Complementary gain-of-function experiments were performed by adoptively transferring lymphocyte subsets to validate their contribution to tissue repair in wounded SCID mice. Results: CD4 + T lymphocytes were present within dermal wounds of WT mice beginning on day 1 and remained through day 30. Wounds of SCID mice exhibited accelerated closure, increased inflammation, limited neovascularization, and exacerbated scarring compared with WT mice. Conversely, transfer of either mixed B and T lymphocytes or CD4 + lymphocytes alone into SCID mice resulted in moderated healing with less inflammation, collagen deposition, and scarring than control SCID wounds. In contrast, transfer of other lymphocyte subsets, including helper T lymphocytes (CD3 + CD4 + CD25 − ), CD8 + T cells and B cells, or regulatory T lymphocytes (CD4 + CD25 + CD127 low ), did not reduce scar. Innovation: The finding that lymphocytes delay wound healing but reduce scar...