Natural variation of macrophage activation as disease-relevant phenotype predictive of inflammation and cancer survival.
Nat Commun
; 8: 16041, 2017 07 24.
Article
em En
| MEDLINE
| ID: mdl-28737175
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-12ß 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Variação Genética
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Modelos Animais
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Ativação de Macrófagos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article