Obesity compromises the ability of skin γδ T cells to regulate skin homeostasis and barrier function (166.6)

Abstract

Abstract Within the epidermis of the skin resides a unique population of γδ T lymphocytes that play key roles in skin homeostasis and wound repair. During obesity and related metabolic disease the skin-resident γδ T lymphocytes become dysfunctional due the chronic inflammatory environment. This dysfunction contributes to the non-healing wounds associated with disease. We are now investigating how skin γδ T cell dysfunction impacts normal keratinocyte homeostasis. Interestingly, in lean mice we have determined that the number of keratinocytes in the epidermis is directly proportional to the number of closely neighboring γδ T cells. Once obesity and related metabolic disease ensues, the keratinocyte numbers resemble areas that are devoid of γδ T cells in lean mice and keratinocytes are unable to maintain normal homeostatic numbers. Furthermore, keratinocytes in obese mice exhibit diminished proliferation and accelerated differentiation. This results in a dysregulated epidermis in which fewer basal keratinocytes express the proliferation marker keratin 5 and more exhibit early expression of the differentiation marker keratin 1. Additionally, skin γδ T cells downregulate CD103 in obese mice, while keratinocytes alter expression of its ligand E-cadherin. Together these studies demonstrate that dysfunctional γδ T cells in the epidermis of obese mice contribute to impaired keratinocyte homeostasis ultimately resulting in compromised skin barrier function.