Mannose Metabolism Is Essential for Th1 Cell Differentiation and IFN-γ Production

Glucose-derived mannose is a common component of glycoproteins, and its deficiency leads to a severe defect in protein glycosylation and failure in basic cell functions. In this work, we show that mannose metabolism is essential for IFN-γ production by mouse Th1 cells. In addition, we demonstrate that the susceptibility of Th1 cells to glycolysis restriction depends on the activation conditions and that under diminished glycolytic flux, mannose availability becomes the limiting factor for IFN-γ expression. This study unravels a new role for glucose metabolism in the differentiation process of Th1 cells, providing a mechanistic explanation for the importance of glycolysis in immune cell functions.