210 Chapter 7 ABSTRACT Thermal injury often causes excessive and long-lasting inflammation that complicates recovery of patients. There is a lack of appropriate, animal-free models to study the inflammatory processes after burn injury and develop more effective therapies to improve burn care and outcome. Here, we created a human full skin equivalent (FSE) burn wound model in which human peripheral blood derived monocytes and T cells were incorporated. These cells are involved in the innate and adaptive immune response to burn injury. Monocytes in the FSEs differentiated into macrophages. Percentage of HLA-DR+ macrophages and production of cytokines such as IL-1β, IL-6, IL-8 (CXCL8) and IL-12p70 were increased in burn-injured FSEs compared to uninjured FSEs. A portion of T cells actively migrated into the FSE and highly expressed CD25. T cells in the FSE also showed increased expression of markers related to regulatory T cell, Th1 or Th17 activity, coinciding with increased production of cytokines such as IFN-γ, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IP-10 (CXCL10) and TGF-β1. Burn injury did not affect the studied T cell markers, but the levels of IL-10 and IP-10 were decreased. In this pilot study, we set the first steps to develop an immunocompetent skin model for the study of burn-induced innate and adaptive immune reactions, reducing the need for experimental animals.
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