ArrayExpress Uploader03702unstimulatedMacrophageunstimulatedMonocyteunstimulatedMacrophageunstimulatedMonocytestimulated with FlagellinMacrophagestimulated with FlagellinMonocytearrayexpress_sid4Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory...20388715E-GEOD-22373/profile/8773/arrayexpressuploader26cytokineinterleukinmucosastromaDec.12, 2014Falsemonocyte-vs-macrophage-studyE-GEOD-22373_A-AFFY-44Monocyte vs Macrophage StudySep.15, 2014Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3-TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon beta, which together mediate all TLR MyD88-dependent and -independent NF-kappaB signaling, did not phosphorylate NF-kappaB p65 or Smad-induced IkappaBalpha, and did not translocate NF-kappaB into the nucleus. Importantly, transforming growth factor-beta released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-kappaB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-beta-induced dysregulation of NF-kappaB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages. Comparison of unstimulated monocytes and macrophages, and flagellin stimulated monocytes and macrophages.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-22373humanhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-22373/samples/