Proprotein convertase furin is preferentially expressed in T helper 1 cells and regulates interferon gamma

Abstract
Interleukin 12 (IL-12) is a major inducer of interferon gamma (IFN-γ) and the principal mediator of T helper 1 (Th1) differentiation. To identify IL-12–regulated genes, which might contribute to Th1 differentiation and IFNG regulation, we employed microarray analysis. Surprisingly, a ubiquitously expressed proprotein convertase (PC), furin, was one of the most consistently IL-12–induced genes in T cells, and among PCs was the only one regulated by this cytokine. Furin was preferentially expressed in differentiated Th1 cells in a Stat4-dependent manner. Expression of furin enhanced IFN-γ secretion, whereas inhibition of furin interfered with IFN-γ production. Thus, we conclude that IL-12 induction of furin might represent a new aspect of IFN-γ regulation and control of Th1 differentiation.