D-Mannose Suppresses æ T Cells and Alleviates Murine Psoriasis

Psoriasis is a chronic skin disorder associated with multiple sequelae, such as psoriatic arthritis and cardiovascular diseases. Increasing evidence has shown that gamma delta T cells, as sources of IL-17A, play critical roles in psoriatic inflammations. However, there still lack effective ways to manipulate these pathogenic gamma delta T cells, which are less well studied than alpha beta T cells. The present study aims to characterize the phenotype of gamma delta T cells and evaluate the impact of D-mannose (a C-2 epimer of glucose) on gamma delta T cell-mediated psoriasis. We found that skin-draining LN gamma delta T cells underwent robust proliferation and acquired an IL-17-producing phenotype during psoriasis. The transcriptomic profiles of these psoriatic gamma delta T cells had elevated glycolytic signatures. Importantly, D-mannose treatment suppressed the gamma delta T cell reaction and successfully alleviated the local and systematic inflammation induced by imiquimod. The decreased AKT/mTOR/HIF-1 alpha signaling and glycolytic ability may contribute to the suppression of gamma delta T cells achieved by D-mannose. Our study increased understanding of gamma delta T cells in psoriasis and promoted D-mannose utilization as a potential clinical application for autoimmune diseases driven by gamma delta T cells.