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

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 FcγR 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.