Characterising interleukin-27 (IL-27) responses in human blood derived macrophage cells

Macrophages are key cells in the pathogenesis of chronic inflammatory diseases. Interleukin (IL)-27 is a pleiotropic cytokine with mostly immunoregulatory functions and associated with a wide array of diseases. There is little knowledge on the effects of IL-27 on human macrophages. Here, we characterise the effect of IL-27 on human blood derived CD14+ monocyte derived macrophages (MDMs), in resting state and under inflammatory stimulation (+LPS/PepG), through targeted transcriptomic expression profile, phagocytosis of E. coli bioparticles and expression of intracellular and secreted proteins by DIA mass spectrometry and multiplex ELISA, respectively. There was no change in pro-inflammatory cytokine gene expression with IL-27. IL-27 led to changes in the chemokine secretome, inducing a significant upregulation of the chemokines CXCL9 and CXCL10 and reduced expression of CCL2, CCL7, CCL13, CCL18, CCL24, CXCL13, IL-10 and Midkine. Macrophage phagocytosis was not affected by IL-27. IL-27 effects on intracellular proteome were subtle overall. Using unadjusted p values, changes were most pronounced in the resting state, with a significant (p < 0.05) increase in 106 and decrease in 11 proteins. Enrichment analysis suggested regulation of several biological processes by IL-27, including cellular response to type II interferon. Overall, we demonstrate novel biology of IL-27 mediated effects in human macrophages.