D-mannose suppressed ?d T cells and alleviated murine psoriasis.

Psoriasis is a chronic skin suffering with multiple comorbidities such as psoriatic arthritis and cardiovascular diseases. Increasing evidences have shown the ?d T cells as the sources of IL-17A play critical roles in the psoriatic syndrome. However, there is still lack an effective way to manipulate these pathogenic ?d T cells which were less studied relative to ab T cells. The present study aims to characterize the phenotype of ?d T cells and evaluate the impact of D-mannose (a C-2 epimer of glucose) on ?d T-mediated psoriasis. We found the psoriatic ?d T cells underwent robust proliferation and acquired an IL-17 producing phenotype. The transcriptomic profiles of these skin draining LN ?d T cells had elevated glycolytic features. Importantly, Treatment of D-mannose inhibited ?d T cells and successfully alleviated the local and systematic inflammations induced by imiquimod. The decreased AKT/mTOR/HIF-1a signaling and glycolytic ability may contribute to the suppression of ?d T cells achieved by mannose. Our study deepened the understandings of ?d T cells in psoriasis, meanwhile, promoted D-mannose utilization as a potent clinical application for ?d T cells driven autoimmune diseases. Overall design: mRNA profiles of ?d T cells from skin draining LN and spleen of healthy and psoriatic mice.