Dendritic epidermal T cells secreting exosomes promote the proliferation of epidermal stem cells to enhance wound re-epithelialization

Background Efficient re-epithelialization is important for successful skin wound healing. The proportion of epidermal stem cells (EpSCs) and dendritic epidermal T cells (DETCs) determines the extent of wound re-epithelialization, especially in large areas of skin tissue loss. However, it remains unk...
Ausführliche Beschreibung

Background Efficient re-epithelialization is important for successful skin wound healing. The proportion of epidermal stem cells (EpSCs) and dendritic epidermal T cells (DETCs) determines the extent of wound re-epithelialization, especially in large areas of skin tissue loss. However, it remains unknown whether and how DETCs regulate the status of EpSCs to impact wound re-epithelialization. Methods To investigate how DETCs regulate EpSCs in skin re-epithelialization, we utilized normal or full-thickness skin deficient wide type (WT) mice and Tcrσ knockout ($ Tcrσ^{−/−} $) mice with DETCs or DETCs-derived exosomes (Exos) treatment. Flow cytometry analysis (FCAS), BrdU labelled experiments, immunofluorescence and immunohistochemical assays were performed to detect the proportion of EpSCs in the epidermis. Wound closure rate and re-epithelialization were assayed by a macroscopical view and hematoxylin–eosin (H&E) staining. EpSCs in vitro were co-cultured with DETCs in a transwell-dependent or -independent manner, or supplement with GW4869 or Exos (5 µg/mL, 15 µg/mL and 45 µg/mL), and the proliferation of EpSCs was detected by means of FCAS and CFSE. Results Our data showed that the proportion of $ CD49f^{bri} %$ CD71^{dim} $ cells, $ K15^{+} $ cells and $ BrdU^{+} $ cells in the normal epidermis of $ Tcrδ^{−/−} $ mice had no significant difference compared to WT mice. For wounded $ Tcrδ^{−/−} $ mice, DETCs treatment increase the proportion of $ CD49f^{bri} %$ CD71^{dim} $ cells, $ K15^{+} $ cells and $ BrdU^{+} $ cells in the epidermis around the wound in comparison to PBS treatment. DETCs significantly increased the number of $ CD49f^{bri} %$ CD7^{dim} $ cells and $ K15^{+} $ cells through transwell-dependent or -independent manners relative to control group. Furthermore, Exos stimuli remarkedly promote the proliferation of EpSCs compared to control group, while the increasement was suppressed when DETCs were interfered with GW4869. Gross observation and H&E staining showed that Exos significantly accelerated wound closure and increased re-epithelialization length in $ Tcrδ^{−/−} $ mice when compared to control mice. Additionally, we found in vivo that Exos observably facilitated the proliferation of $ CD49f^{bri} %$ CD7^{dim} $ cells and $ K15^{+} $ cells. Conclusions We revealed that DETCs enhanced the proliferation of EpSCs in the epidermis around the wounds to accelerate re-epithelialization in which Exos played important roles in the remote regulation of EpSCs proliferation. Together, these findings suggest a mechanistic link among DETC-derived exosomes, the proliferation of EpSCs, and wound re-epithelialization in the skin. Ausführliche Beschreibung

Autor*in:	Liu, Mian [verfasserIn] Liu, Zhihui Chen, Yunxia Peng, Shiya Yang, Jiacai Chen, Cheng Wang, Jue Shang, Ruoyu Tang, Yuanyang Huang, Yong Zhang, Xiaorong Hu, Xiaohong Liou, Yih-Cherng Luo, Gaoxing He, Weifeng

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Epidermal stem cells Proliferation Re-epithelialization Dendritic epidermal T cells Exosomes

Anmerkung:	© The Author(s) 2022

Übergeordnetes Werk:	Enthalten in: Stem cell research & therapy - London : BioMed Central, 2010, 13(2022), 1 vom: 21. März
Übergeordnetes Werk:	volume:13 ; year:2022 ; number:1 ; day:21 ; month:03

Links:	Volltext

DOI / URN:	10.1186/s13287-022-02783-6

Katalog-ID:	SPR050577867