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

J Cell Sci. 2020 Apr 23;134(5):jcs246421. doi: 10.1242/jcs.246421.

Abstract

Protein tyrosine phosphatase 1B (PTP1B, also known as PTPN1) is a negative regulator of the leptin and insulin signalling pathways. This phosphatase 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 that 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 the proinflammatory cytokines TNFα and IL6 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.

Keywords: Cytokine secretion; Cytomegalovirus; Herpesvirus; Innate immunity; Pattern recognition receptor; RIG-I; STING; TLR; Type I IFN; UNC93B; cGAS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Insulin
  • Interferon Type I* / genetics
  • Mice
  • Mice, Knockout
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1* / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1* / metabolism
  • Signal Transduction
  • Virus Diseases* / immunology

Substances

  • Insulin
  • Interferon Type I
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Ptpn1 protein, mouse