Natural variation of macrophage activation as disease-relevant phenotype predictive of inflammation and cancer survival

Konrad Buscher, Erik Ehinger, Pritha Gupta, Akula Bala Pramod, Dennis Wolf, George Tweet, Calvin Pan, Charles D. Mills, Aldons J. Lusis, Klaus Ley

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Although mouse models exist for many immune-based diseases, the clinical translation remains challenging. Most basic and translational studies utilize only a single inbred mouse strain. However, basal and diseased immune states in humans show vast inter-individual variability. Here, focusing on macrophage responses to lipopolysaccharide (LPS), we use the hybrid mouse diversity panel (HMDP) of 83 inbred strains as a surrogate for human natural immune variation. Since conventional bioinformatics fail to analyse a population spectrum, we highlight how gene signatures for LPS responsiveness can be derived based on an Interleukin-12β and arginase expression ratio. Compared to published signatures, these gene markers are more robust to identify susceptibility or resilience to several macrophage-related disorders in humans, including survival prediction across many tumours. This study highlights natural activation diversity as a disease-relevant dimension in macrophage biology, and suggests the HMDP as a viable tool to increase translatability of mouse data to clinical settings.

Original languageEnglish (US)
Article number16041
JournalNature communications
Volume8
DOIs
StatePublished - Jul 24 2017
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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