Beschreibung:
<jats:title>Abstract</jats:title><jats:p>IL‐27 is a cytokine of the IL‐12 family, composed of EBI3 and IL‐27p28. IL‐27 regulates immune responses and also other physiological processes including hematopoiesis, angiogenesis, and bone formation. Its receptor, composed of IL‐27Rα and gp130, activates the STAT pathway. Here, we show that different glycosaminoglycans (GAGs) modulate human IL‐27 activity in vitro. We find that soluble heparin and heparan sulfate efficiently inhibit human IL‐27 activity as shown by decreased STAT signaling and downstream biological effects. In contrast, membrane‐bound heparan sulfate seems to positively regulate IL‐27 activity. Our biochemical studies demonstrate that soluble GAGs directly bind to human IL‐27, consistent with in silico analyses, and prevent its binding to IL‐27Rα. Although murine IL‐27 also bound to GAGs in vitro, its activity was less efficiently inhibited by soluble GAGs. Lastly, we show that two heparin‐derivatives, low molecular weight heparin and fondaparinux, that like unfractionated heparin are used in clinics, had weaker or no effect on human IL‐27 activity. Together, our data identify GAGs as new players in the regulation of human IL‐27 activity that might act under physiological conditions and may also have a clinical impact in heparin‐treated patients.</jats:p>