Granulocytes Are Unresponsive to IL-6 Due to an Absence of gp130
Andrew N Wilkinson, Kate H Gartlan, Greg Kelly, Luke D Samson, Stuart D Olver, Judy Avery, Nienke Zomerdijk, Siok-Keen Tey, Jason S Lee, Slavica Vuckovic, Geoffrey R Hill
The Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2018
IL-6 mediates broad physiological and pathological effects through its receptor signal transducing unit gp130. Due to the reportedly wide cellular expression of gp130, IL-6 is thought to signal ubiquitously via gp130 complex formation with membrane-bound IL-6Rα or soluble IL-6Rα. gp130 signaling primarily induces p-STAT3 and p-STAT1. In contrast to the previous dogma, we show in this article that circulating mouse and human granulocytes are unable to induce p-STAT3 or p-STAT1 after stimulation with IL-6 or an IL-6/soluble IL-6R complex. Furthermore, we demonstrate that this is due to a lack of gp130 expression on mouse and human granulocytes, despite their expression of membrane-bound IL-6R...View full abstract
This work was supported by research grants from the National Health and Medical Research Council (Australia). G.R.H. is a National Health and Medical Research Council Senior Principal Research Fellow.