Skin Resident γδ T Cell Function and Regulation in Wound Repair.

The skin is a critical barrier that protects against damage and infection. Within the epidermis and dermis reside γδ T cells that play a variety of key roles in wound healing and tissue homeostasis. Skin-resident γδ T cells require T cell receptor (TCR) ligation, costimulation, and cytokine reception to mediate keratinocyte activity and inflammatory responses at the wound site for proper wound repair. While both epidermal and dermal γδ T cells regulate inflammatory responses in wound healing, the timing and factors produced are distinct. In the absence of growth factors, cytokines, and chemokines produced by γδ T cells, wound repair is negatively impacted. This disruption in γδ T cell function is apparent in metabolic diseases such as obesity and type 2 diabetes. This review provides the current state of knowledge on skin γδ T cell activation, regulation, and function in skin homeostasis and repair in mice and humans. As we uncover more about the complex roles played by γδ T cells in wound healing, novel targets can be discovered for future clinical therapies.

Arylphosphonium salts interact with DNA to modulate cytotoxicity.

Arylphosphonium salts (APS) are compounds that have both lipophilic and cationic character, allowing them facile transport through plasma membranes or cell walls to accumulate in the cytoplasm or mitochondria of cells. APS molecules preferentially accumulate in tumor cells and are therefore under investigation as tumor imaging agents and mitochondrial targeting molecules. We have generated a systematic set of APS to study their ability to associate with DNA. The chemical structure of the APS determines the extent of its interaction with DNA and therefore its ability to aggregate the DNA. Also, APS compounds blocked DNA amplification in vitro at concentrations below the aggregation threshold, corroborating the structure/interaction relationship. Furthermore, the extent of APS:DNA interaction strongly correlates with bacterial toxicity, implying that APS molecules may deter cellular metabolic DNA pathways. Finally, DNA repair deficient and DNA bypass polymerase deficient bacterial strains were screened for sensitivity to APS. Interestingly, no single pathway for the repair or tolerance of these compounds was solely responsible for APS mediated toxicity. Taken together, these findings suggest that APS compounds may be capable of targeting and regulating unchecked cell growth and therefore show potential applications as a chemotherapeutic agent.