Recent Developments in the Role of Protein Tyrosine Phosphatase 1B (PTP1B) as a Regulator of Immune Cell Signalling in Health and Disease

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is a non-receptor tyrosine phosphatase best known for its role in regulating insulin and leptin signalling. Recently, knowledge on the role of PTP1B as a major regulator of multiple signalling pathways involved in cell growth, proliferation, viability and metabolism has expanded, and PTP1B is recognised as a therapeutic target in several human disorders, including diabetes, obesity, cardiovascular diseases and hematopoietic malignancies. The function of PTP1B in the immune system was largely overlooked until it was discovered that PTP1B negatively regulates the Janus kinase-a signal transducer and activator of the transcription (JAK/STAT) signalling pathway, which plays a significant role in modulating immune responses. PTP1B is now known to determine the magnitude of many signalling pathways that drive immune cell activation and function. As such, PTP1B inhibitors are being developed and tested in the context of inflammation and autoimmune diseases. Here, we provide an up-to-date summary of the molecular role of PTP1B in regulating immune cell function and how targeting its expression and/or activity has the potential to change the outcomes of immune-mediated and inflammatory disorders.

Keywords: disease; haematopoiesis; immune cells; inflammation; protein tyrosine phosphatase 1B (PTP1B); signalling.

Figure 1

The role of PTP1B in immune cell function. PTP1B regulates the activation and functional properties of both innate and adaptive immune cells. The pharmacological inhibition (↑, ↓) [32,33,34,35] or knockout (↑, ↓) [12,22,29,35,36,37,38,39,40,41,42,43,44,45] of PTP1B can alter their functional properties, as shown by the arrows. The results refer to global knockout unless specified by an asterisk (*), which represents cell-specific knockout.

Figure 2

Therapeutic potential of PTP1B inhibition in immune-mediated diseases. Inhibiting PTP1B in immune-mediated diseases could have potential therapeutic effects. It can improve the outcome of disease (in green) by suppressing the pro-inflammatory phenotype of immune cells in autoimmune diseases, or it can help recruit immune cells to the site of infection and promote their activation. This, however, can be harmful in the context of other diseases (in red), exacerbating inflammation and promoting disease progression [25,29,33,36,44,49,57,60,61,62,63,64,65,66,67,68,69,70].