Dataset Information

Differential Responsiveness of Monocyte and Macrophage Subsets to Interferon.

ABSTRACT:

Objective

Peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients exhibit a gene expression program (interferon [IFN] signature) that is attributed to overproduction of type I IFNs by plasmacytoid dendritic cells. Type I IFNs have been thought to play a role in the pathogenesis of SLE. This study was undertaken to examine an unexpected influence of monocyte/macrophages on the IFN signature.

Methods

Proinflammatory (classic) and antiinflammatory (nonclassic) monocyte/macrophages were sorted from mice and analyzed by RNA sequencing and quantitative polymerase chain reaction (qPCR). Type I IFN-?/?/? receptor (IFNAR-1) expression was determined by qPCR and flow cytometry. Macrophages were stimulated in vitro with IFN?, and pSTAT1was measured.

Results

Transcriptional profiling of peritoneal macrophages from mice with pristane-induced SLE unexpectedly indicated a strong IFN signature in classic, but not nonclassic, monocyte/macrophages exposed to the same type I IFN concentrations. Ifnar1 messenger RNA and IFNAR surface staining were higher in classic monocyte/macrophages versus nonclassic monocyte/macrophages (P < 0.0001 and P < 0.05, respectively, by Student's t-test). Nonclassic monocyte/macrophages were also relatively insensitive to IFN?-driven STAT1 phosphorylation. Humans exhibited a similar pattern: higher IFNAR expression (P < 0.0001 by Student's t-test) and IFN?-stimulated gene expression (P < 0.01 by paired Wilcoxon's rank sum test) in classic monocyte/macrophages and lower levels in nonclassic monocyte/macrophages.

Conclusion

This study revealed that the relative abundance of different monocyte/macrophage subsets helps determine the magnitude of the IFN signature. Responsiveness to IFN? signaling reflects differences in IFNAR expression in classic (high IFNAR) compared to nonclassic (low IFNAR) monocyte/macrophages. Thus, the IFN signature depends on both type I IFN production and the responsiveness of monocyte/macrophages to IFNAR signaling.

SUBMITTER: Han S

PROVIDER: S-EPMC6935410 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Differential Responsiveness of Monocyte and Macrophage Subsets to Interferon.

Han Shuhong S Zhuang Haoyang H Lee Pui Y PY Li Mingjia M Yang Lijun L Nigrovic Peter A PA Reeves Westley H WH

Arthritis & rheumatology (Hoboken, N.J.) 20191210 1

<h4>Objective</h4>Peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients exhibit a gene expression program (interferon [IFN] signature) that is attributed to overproduction of type I IFNs by plasmacytoid dendritic cells. Type I IFNs have been thought to play a role in the pathogenesis of SLE. This study was undertaken to examine an unexpected influence of monocyte/macrophages on the IFN signature.<h4>Methods</h4>Proinflammatory (classic) and antiinflammatory (n ...[more]

PMID: 31390156

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Dataset Information

Differential Responsiveness of Monocyte and Macrophage Subsets to Interferon.

Objective

Methods

Results

Conclusion

Publications

Differential Responsiveness of Monocyte and Macrophage Subsets to Interferon.

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