Drug suspending during wound healing effectively weakens immunosuppression-related complications by preserving CD8+ T cell function

Immunosuppressive medications, which interfere with the activation and proliferation of T and B cells, increase the risk of wound healing complications. To address it, this study aimed to validate the feasibility of drug suspending during wound healing, whilst exploring the mechanisms exerted by T cells, which are important in the wound healing process. For this, a mouse skin wound model was set up. Tacrolimus and fingolimod were both administered intraperitoneally prior to wounding to inhibit the T cell activation and migration, respectively. Flow-cytometric analysis subsequently revealed the functional T cell subtypes detected during the healing process. A CD8a antibody was also administered to deplete CD8⁺ T cells in vivo to verify their specific function. It was found that tacrolimus or fingolimod administration delayed the early phase of wound healing by reducing collagen production, which was also supported by the downregulation of col1a1, col3a1, and tgfb1. However, there was no significant difference in the total healing period. Both spleen- and skin-derived CD8⁺ T cells were proliferated and activated after injury without intervention, whereas CD4⁺ T cells showed no significant changes. Furthermore, selectively depleting CD8⁺ T cells retarded the healing process by downregulating collagen production-associated genes (col1a1, col3a1, tgfβ1, and en1) and proteins (collagen type 1 and 3). In addition, the CD8a antibody decreased the expression of genes lta, tnfa, il13, and il13ra, and protein IL-13Rα. In conclusion, suspending immunosuppressive drugs during wound healing was shown to be feasible through restraining the migration of activated T cells. CD8⁺ T cells represented the primary functional subtype positively associated with wound healing. This article is protected by copyright. All rights reserved.

CD8+ T cell; T cell; drug suspending; immunosuppression; wound healing.