Generally, wounds heal through either scar formation or tissue regeneration. Scar formation is more common in adult mammals and leads to loss of normal tissue architecture and function. Past research from our lab studied how aged mice and imiquimod-treated mice showed improved tissue regeneration compared to young mice and untreated mice. Our goal is to study the mechanisms behind scar formation in order to discover therapeutics that promote skin regeneration.

Using the two mice models for improved tissue regeneration, our lab performed single-cell RNA sequencing to study how the regenerative mice differed from the scarring mice. We identified interesting differences in neutrophil populations and increased CXCR2-CXCL signaling in the scarring mice for further study. Although past groups have studied the role of CXCR2 in wound healing, no consensus has been established on the receptor’s precise role in tissue regeneration.

Recent work from our lab showed that CXCR2 global knockout mice have improved complete ear hole closure compared to wild-type mice. This project's aim is to investigate the role of CXCR2 deficiency in promoting tissue regeneration. Specifically, we want to identify which cell type is responsible for the observed CXCR2 knockout’s regenerative phenotype and what is the role of CXCR2-deficient neutrophils in tissue regeneration.

To study the role of CXCR2 expressed on specific cell types, we used cell-type specific CXCR2 knockout mice using a Cre recombinase system and the ear hole closure model. To determine the role of neutrophils and CXCR2-CXCL signaling in wound healing, we performed immunofluorescence on the tissue collected from the edge of the ear punch. Flow cytometry was conducted to quantify neutrophil recruitment in CXCR2 knockout mice during the healing process. The project’s future directions include continuing to study the role of CXCR2-deficient neutrophils on regeneration and finding a potential mechanism behind this regenerative phenotype.