A Comprehensive Atlas of Immunological Differences Between Humans, Mice, and Non-Human Primates.
A Comprehensive Atlas of Immunological Differences Between Humans, Mice, and Non-Human Primates.
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DOI：
10.3389/fimmu.2022.867015
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发表时间：
2022
影响因子：
7.3
通讯作者：
Nolan GP
中科院分区：
文献类型：
--
作者：
Bjornson-Hooper ZB;Fragiadakis GK;Spitzer MH;Chen H;Madhireddy D;Hu K;Lundsten K;McIlwain DR;Nolan GP
动物模型是药物开发和评估过程中不可或缺的一部分。然而，它们是人类的不完美反映，并且许多免疫学差异的程度和性质是未知的。随着靶向治疗和生物治疗的兴起，了解人类和模式生物免疫学行为的分子差异变得越来越重要。然而，针对非人灵长类动物抗原的抗体很少，而且物种之间交叉反应性的数据库也不完整。因此，我们在来自人类和四种非人灵长类动物物种的血液中的五种免疫细胞群体中筛选了332种抗体，产生了包括细胞类型特异性的全面交叉反应性目录。我们使用该目录创建了用于人类的大型流式细胞术通用跨物种表型和信号传导面板，沿着三种与人类最相似的模型生物：恒河猴和食蟹猴和非洲绿色猴;以及药物开发中最广泛使用的哺乳动物模型之一：C57 BL/6小鼠。作为原理证明，我们使用质谱仪测量了所有五个物种对15种刺激的免疫细胞信号传导反应。我们发现了许多不同的细胞表型和免疫信号事件发生在物种内和物种之间的情况下，并详细介绍了三个例子（双阳性T细胞频率和信号;粒细胞对炭疽杆菌抗原的反应;和B细胞亚群）。我们还探讨了猴疱疹B病毒血清状态与免疫特征的相关性。抗体面板和生成的完整数据集可在线作为资源，以使未来的研究在治疗评估期间比较不同物种的免疫反应。
Animal models are an integral part of the drug development and evaluation process. However, they are unsurprisingly imperfect reflections of humans, and the extent and nature of many immunological differences are unknown. With the rise of targeted and biological therapeutics, it is increasingly important that we understand the molecular differences in the immunological behavior of humans and model organisms. However, very few antibodies are raised against non-human primate antigens, and databases of cross-reactivity between species are incomplete. Thus, we screened 332 antibodies in five immune cell populations in blood from humans and four non-human primate species generating a comprehensive cross-reactivity catalog that includes cell type-specificity. We used this catalog to create large mass cytometry universal cross-species phenotyping and signaling panels for humans, along with three of the model organisms most similar to humans: rhesus and cynomolgus macaques and African green monkeys; and one of the mammalian models most widely used in drug development: C57BL/6 mice. As a proof-of-principle, we measured immune cell signaling responses across all five species to an array of 15 stimuli using mass cytometry. We found numerous instances of different cellular phenotypes and immune signaling events occurring within and between species, and detailed three examples (double-positive T cell frequency and signaling; granulocyte response to Bacillus anthracis antigen; and B cell subsets). We also explore the correlation of herpes simian B virus serostatus on the immune profile. Antibody panels and the full dataset generated are available online as a resource to enable future studies comparing immune responses across species during the evaluation of therapeutics.
影响因子：
0.7
作者：
Brown KN;Barratt-Boyes SM
通讯作者：
Barratt-Boyes SM