IL-6 signaling as a driver of self-renewal and alternative activation of adipose tissue macrophages

Obesity is associated with chronic low grade inflammation of adipose tissue and an increase of AT macrophages that is linked to the onset of type 2diabetes. We have recently shown that neutralization of interleukin 6 in AT organ cultures inhibits proliferation of AT macrophages, which is limited to the alternatively activated macrophage phenotype. In this study, we tested the effects of myeloid cell specific IL6Ra deficiency on the metabolic phenotype, AT macrophages polarization and proliferation after 20 weeks of HFD in vivo. Obese mice showed no differences in insulin sensitivity or histological markers of AT inflammation. Notably, we found a reduction in AT macrophages number expressing the mannose receptor CD206, a putative marker for antiinflammatory M2 macrophages, as well as a decrease in proliferation marker Ki67 in AT macrophages lacking the IL6Ra subunit. Importantly, BMDM data of IL4Ra knockout mice revealed that IL6 mediated effects on Mrc1 gene expression are independent from the IL6 IL4Ra axis.