Longitudinal Analysis of Disease-Site Activities Impairing Wound Healing in Epidermolysis Bullosa and Development of Therapeutic Strategies
Abstract
Development of chronic wounds is very common for patients affected by hereditary Epidermolysis Bullosa (EB). To date, there is still a substantial gap in understanding of the cellular events occurring during progression of wounds from early to poorly healing, and chronic wounds. To understand the dynamics of the inflammatory infiltrates at EB skin wounds and, possibly, delineate leukocytic cells, which are responsible for stalled wound repair, we conducted comprehensive FACS-based assessment of leukocytic populations associated with different stages of EB wound progression. Our analysis has determined that EB skin wound bed is associated with CD11c+ antigen presenting cells (20 percent), CD11b+ mature neutrophils (38 percent) and macrophages (7 percent), and T cells (40 percent). Remarkably, the majority of CD11c+ antigen presenting cells (80 percent), including CD207+ Langerhans cells, express CD80 activation marker and the majority of the CD4+ and CD8+ T cells are represented by CD45RO+ effector T cells. In addition, our data demonstrated activation of adaptive immunity toward bacterial antigens in EB-associated wounds, immune-mediated targeting of infected host cells, and Treg-mediated inhibition of T cell responses toward bacterial antigens. Our findings suggest that adaptive immunity plays an important role in clearing bacterial infection in EB wounds.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2019
- Accession Number
- AD1088192
Entities
People
- Olga Igoucheva
Organizations
- Thomas Jefferson University