Glucosamine Interferes With Myelopoiesis and Enhances the Immunosuppressive Activity of Myeloid-Derived Suppressor Cells

Abstract

Glucosamine (GlcN) is the most widely consumed dietary supplement and exhibits anti-inflammatory effects. However, the influence of GlcN on immune cell generation and function is largely unclear. In this study, GlcN was delivered into mice to examine its biological function in hematopoiesis. We found that GlcN promoted the production of immature myeloid cells, known as myeloid-derived suppressor cells (MDSCs), both in vivo and in vitro. Additionally, GlcN upregulated the expression of glucose transporter 1 in hematopoietic stem and progenitor cells (HSPCs), influenced HSPC functions, and downregulated key genes involved in myelopoiesis. Furthermore, GlcN increased the expression of arginase 1 and inducible nitric oxide synthase to produce high levels of reactive oxygen species, which was regulated by the STAT3 and ERK1/2 pathways, to increase the immunosuppressive ability of MDSCs. We revealed a novel role for GlcN in myelopoiesis and MDSC activity involving a potential link between GlcN and immune system, as well as the new therapeutic benefit.

Pharmacological modulation of myeloid-derived suppressor cells to dampen inflammation

“…Glucosamine is an essential substrate for the glycosylation of proteins and lipids. Recently, glucosamine was shown to promote the generation of MDSCs from murine bone marrow cells in vitro as well as in mice treated for 14 days with intraperitoneal injections of glucosamine ( 58 ). Furthermore, glucosamine also increased MDSC activity confirmed by T cell suppression assays and increased levels of Arg-1 and iNOS expression ( 58 ).…”

“…Recently, glucosamine was shown to promote the generation of MDSCs from murine bone marrow cells in vitro as well as in mice treated for 14 days with intraperitoneal injections of glucosamine ( 58 ). Furthermore, glucosamine also increased MDSC activity confirmed by T cell suppression assays and increased levels of Arg-1 and iNOS expression ( 58 ). Further analysis showed this effect was likely mediated via the STAT3 and ERK1/2 pathways ( 58 ).…”

“…Furthermore, glucosamine also increased MDSC activity confirmed by T cell suppression assays and increased levels of Arg-1 and iNOS expression ( 58 ). Further analysis showed this effect was likely mediated via the STAT3 and ERK1/2 pathways ( 58 ).…”