Up-regulation of BTN3A1 on CD14(+) cells promotes V gamma 9V delta 2 T cell activation in psoriasis

V gamma 9V delta 2 T cells play an important role in the development and progression of psoriasis vulgaris (PV), but how they promote skin inflammation and the molecular mechanisms underlying V gamma 9V delta 2 T cell dysfunction are poorly understood. Here, we show that circulating V gamma 9V delta 2 T cells are decreased and exhibit enhanced proliferation and increased production of IFN-gamma and TNF-alpha in PV patients. Monocytes from PV patients express higher levels of the phosphoantigen sensor butyrophilin 3A1 (BTN3A1) than monocytes from healthy controls. Blockade of BTN3A1 suppresses V gamma 9V delta 2 T cell activation and abolishes the difference in V gamma 9V delta 2 T cell activation between PV patients and healthy controls. The CD14(+) cells in PV skin lesions highly express BTN3A1 and juxtapose to V delta 2 T cells. In addition, IFN-gamma induces the up-regulation of BTN3A1 on monocytes. Collectively, our results demonstrate a crucial role of BTN3A1 on monocytes in regulating V gamma 9V delta 2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis.