Immune complex-driven generation of human macrophages with anti-inflammatory and growth-promoting activity

The goal of this study was to characterize and examine gene expression programs in a population of anti-inflammatory human macrophages that were generated by TLR stimulation in the presence of immune complexes. We conducted high-resolution sequencing of the transcriptomes of macrophages in vitro at 4 hours post-stimulation using an RNA-seq approach. An array of computational tools was applied to map reads to the human genome. mRNA abundance was determined for human genes to explain the influence of a secondary reprogramming signal (immune complexes signaling via Fc?R ligation) on macrophage transcriptional responses. Resting human macrophages were compared to macrophages stimulated with LPS alone (LPS), or LPS along with immune complexes (LPS+IC). For these studies, human monocyte-derived macrophages were differentiated in culture in M-CSF, rested overnight, then stimulated with LPS or LPS + IC. Our data show that Fc?R cross-linking on TLR-stimulated human macrophages fundamentally changes transcriptional programs. We identify novel targets for further research to understand the functionality of this macrophage population.