ID: 143: Characterization of IL-6-type cytokine receptor expression during DC maturation and activation

Abstract

Interleukin-6 (IL-6) is a regulator of cell growth and differentiation as well as hematopoiesis, immune response and inflammation. The classical IL-6 receptor complex consists of the membrane-bound, non-signal transducing IL-6 receptor alpha chain (IL-6R α ) and the transmembrane, signal transducing subunit glycoprotein 130 (gp130). Gp130 is ubiquitously expressed; the IL-6R α expression is limited to immune cells and hepatocytes. Dendritic cells (DCs) are key players of immune responses and express both gp130 and IL-6R α . As professional antigen-presenting cells they stimulate naive T cells upon activation by microbial stimuli or tissue destruction. DC maturation and activation is regulated by numerous cytokines and transcription factors, including IL-6 and STAT3. Experiments with IL-6 knock-out mice as well as gp130 knock-in mice revealed that IL-6 inhibits DC maturation and further, plays an important role to keep DC in an immature state in the absence of infection. Studies in bone marrow-derived DCs (BMDCs) also provide evidence that IL-6 signaling can directly inhibit LPS-induced BMDC maturation/activation via STAT3 activation. Although these results suggest that IL-6 is an important regulator of the DC lineage, little is known about the expression/regulation of its receptor subunits during DC maturation/activation. In the present study, we found that IL-6R α and gp130 expression increase during maturation of BMDCs from MHCIIlowCD11clow to MHCIIhighCD11chigh cells. Furthermore, we describe that gp130 cell surface expression is differentially regulated upon BMDC activation using alternative stimuli and that under steady-state conditions different DC subtypes of the spleen exhibit different cell surface expression levels of gp130 and IL-6R α .