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Natural variation of macrophage activation as disease-relevant phenotype predictive of inflammation and cancer survival.
Buscher, Konrad; Ehinger, Erik; Gupta, Pritha; Pramod, Akula Bala; Wolf, Dennis; Tweet, George; Pan, Calvin; Mills, Charles D; Lusis, Aldons J; Ley, Klaus.
Afiliación
  • Buscher K; Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
  • Ehinger E; Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
  • Gupta P; Departments of Medicine, Human Genetics, and Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
  • Pramod AB; Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
  • Wolf D; Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
  • Tweet G; Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
  • Pan C; Departments of Medicine, Human Genetics, and Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
  • Mills CD; BioMedical Consultants, Marine on St. Croix, Minnesota 55047, USA.
  • Lusis AJ; Departments of Medicine, Human Genetics, and Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
  • Ley K; Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Nat Commun ; 8: 16041, 2017 07 24.
Article en En | MEDLINE | ID: mdl-28737175
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Variación Genética / Modelos Animales / Activación de Macrófagos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Variación Genética / Modelos Animales / Activación de Macrófagos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido