Natural variation of macrophage activation as disease-relevant phenotype predictive of inflammation and cancer survival.
Natural variation of macrophage activation as disease-relevant phenotype predictive of inflammation and cancer survival.
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DOI：
10.1038/ncomms16041
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发表时间：
2017-07-24
影响因子：
16.6
通讯作者：
Ley K
中科院分区：
文献类型：
--
作者：
Buscher K;Ehinger E;Gupta P;Pramod AB;Wolf D;Tweet G;Pan C;Mills CD;Lusis AJ;Ley K
尽管存在许多基于免疫的疾病的小鼠模型，但临床转化仍然具有挑战性。大多数基础研究和转化研究只使用单一的近交小鼠品系。然而，人类的基础免疫状态和患病免疫状态表现出巨大的个体差异。在这里，重点关注巨噬细胞对脂多糖（LPS）的反应，我们使用83个近交系的杂交小鼠多样性面板（HMDP）作为人类自然免疫变异的替代品。由于传统的生物信息学无法分析种群谱，因此我们强调了如何根据白细胞介素-12β和精氨酸酶的表达比推导出LPS反应性的基因特征。与已发表的特征相比，这些基因标记在识别人类对几种巨噬细胞相关疾病的易感性或恢复能力方面更为强大，包括预测许多肿瘤的生存。这项研究强调了巨噬细胞生物学中自然激活多样性作为疾病相关维度的重要性，并表明HMDP是一种可行的工具，可以提高小鼠数据在临床环境中的可翻译性。免疫系统的个体间变异广泛影响病理生理。在这里，作者使用杂交小鼠多样性面板作为人类自然免疫变异的替代品，并得出巨噬细胞基因标记与人类对巨噬细胞相关疾病的易感性密切相关。
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. The inter-individual variation of the immune system broadly impacts pathophysiology. Here, the authors use the hybrid mouse diversity panel as a surrogate for human natural immune variation and derive a macrophages gene signature robustly correlating with susceptibility to macrophage-related disorders in humans.
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影响因子：
4.1
作者：
Ceccarelli F;Perricone C;Borgiani P;Ciccacci C;Rufini S;Cipriano E;Alessandri C;Spinelli FR;Sili Scavalli A;Novelli G;Valesini G;Conti F
通讯作者：
Conti F
影响因子：
7.3
作者：
Ley K;Pramod AB;Croft M;Ravichandran KS;Ting JP
通讯作者：
Ting JP
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
64.5
作者：
Brodin P;Jojic V;Gao T;Bhattacharya S;Angel CJ;Furman D;Shen-Orr S;Dekker CL;Swan GE;Butte AJ;Maecker HT;Davis MM
通讯作者：
Davis MM
影响因子：
4.5
作者：
Bennett BJ;Davis RC;Civelek M;Orozco L;Wu J;Qi H;Pan C;Packard RR;Eskin E;Yan M;Kirchgessner T;Wang Z;Li X;Gregory JC;Hazen SL;Gargalovic PS;Lusis AJ
通讯作者：
Lusis AJ