Plasmacytoid Dendritic Cells Regulate Th17 Activation in Diabetic Wound CD4+ T-cells

Abstract

Abstract Introduction: CD4+ T-cell activation is vital for normal wound repair but the factors that control T-cell activation in wounds in vivo are not clear. Our group and others have found increased Th17 activation in diabetic wounds resulting in increased IL-17a and pathologic inflammation that prevents tissue repair. Plasmacytoid dendritic cells (pDC) are antigen presenting cells that are present in early diabetic wound tissue and may play a key role in modulating CD4+ T-cell phenotype. Hence, we hypothesized that diabetic pDCs may influence wound CD4+ T-cells towards Th17 T-cell expansion. Methods: Wild type C57BL/6 mice were fed normal chow diet (13.5% kcal fat; LabDiet) or high fat diet chow (60% kcal fat; Research Diets) for 12–14 weeks to generate the diet-induced obesity (DIO) model of glucose intolerance/insulin resistance. These mice were subsequently wounded, and wound plasmacytoid dendritic cells harvested on day 1 and day 3. These cells were co-cultured with naïve CD4+ T-cells for 3 days, after which T-cell phenotype was determined by flow cytometry. Additionally, pDC in wounds 1-day post wounding were examined by quantitative PCR for cytokine production. Results: Following exposure to DIO pDCs, wild type activated CD4+ T-cells were activated towards a Th17 phenotype via significant increases in TGFb CD4+ T-cell activation and may act to increase inflammation in diabetic wounds.