Protein tyrosine phosphatase 1B (PTP1B) is involved in efficient type I interferon secretion upon viral infection.

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the leptin and insulin signalling pathways. This phosphate is of great interest as PTP1B knockout mice are protected against the development of obesity and diabetes. Here, we provide evidence for a novel function of PTP1B, which is independent of its phosphatase activity, but requires its localisation to the membrane of the endoplasmic reticulum. Upon activation of pattern recognition receptors, macrophages and plasmacytoid dendritic cells from PTP1B knockout mice secrete lower amounts of type I interferon (IFN) than cells from wild type mice. In contrast, secretion of proinflammatory cytokines TNFalpha and IL-6 was unaltered. While PTP1B deficiency did not affect IFNb1 transcription, type I IFN accumulated in macrophages, suggesting a role for PTP1B in mediating secretion of type I IFN. In summary, we have uncovered that PTP1B positively regulates the type I IFN response by promoting secretion of key antiviral cytokines.