title: Genomic analysis of LPS-stimulated myeloid cells identifies a common pro-inflammatory response but divergent IL-10 anti-inflammatory responses.
abstract: Inflammation is an essential physiological response to infection and injury that must be kept within strict bounds. The IL-10/STAT3 anti-inflammatory response (AIR) is indispensable for controlling the extent of inflammation, although the complete mechanisms downstream of STAT3 have not yet been elucidated. The AIR is widely known to extend to other myeloid cells, but it has best been characterized in macrophages. Here we set out to characterize the LPS-mediated pro-inflammatory response and the AIR across a range of myeloid cells. We found that whereas the LPS-induced pro-inflammatory response is broadly similar among macrophages, dendritic cells, neutrophils, mast cells and eosinophils, the AIR is drastically different across all myeloid cell types that respond to IL-10 (all bar eosinophils). We propose a model whereby the IL-10/STAT3 AIR works by selectively inhibiting specific pathways in distinct cell types: in macrophages the AIR most likely works through the inhibition of NF-κB target genes; in DCs and mast cells through indirect IRF disruption; and in neutrophils through IRF disruption and possibly also indirect NF-κB inhibition. In summary, no conserved IL-10/STAT3 AIR effectors were identified; instead a cell type-specific model of the AIR is proposed.
authors.affiliation: 1] Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China [2] World Premier International (WPI) Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, 565-0871 Osaka, Japan.
authors.forename: Andrew Paul
authors.initials: AP
authors.lastname: Hutchins
authors.affiliation: 1] World Premier International (WPI) Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, 565-0871 Osaka, Japan [2] Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin Yoshida, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: 1] World Premier International (WPI) Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, 565-0871 Osaka, Japan [2] Centro de Biología Molecular Severo Ochoa, CSIC/Universidad Autónoma de Madrid, 28049 Madrid, Spain [3] IE Business School, IE University, María de Molina 31 bis, 28006 Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Miranda-Saavedra
mesh_terms: D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; D016753:Interleukin-10