Upregulation of BTN3A1 on CD14+ cells promotes V?9Vd2 T cells activation in psoriasis vulgaris

V?9Vd2 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?9Vd2 T cell dysfunction are poorly understood. Here, we show that circulating V?9Vd2 T cells are decreased and exhibit enhanced proliferation and increased production of IFN-? and TNF-a 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?9Vd2 T cell activation and abolishes the difference in V?9Vd2 T cell activation between PV patients and healthy controls. The CD14+ cells in PV skin lesions highly express BTN3A1 and juxtapose to Vd2 T cells. In addition, IFN-? induces the up-regulation of BTN3A1 on monocytes. Collectively, our results demonstrate a crucial role of BTN3A1 on monocytes in regulating V?9Vd2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis. Overall design: Peripheral V?9Vd2 T cells mRNA profiles of healthy controls (HC) and psoriasis vulgaris (PV) patients