Model-Driven Experimentation: A New Approach to Understand Mechanisms of Tertiary Lymphoid Tissue Formation, Function, and Therapeutic Resolution.
Model-Driven Experimentation: A New Approach to Understand Mechanisms of Tertiary Lymphoid Tissue Formation, Function, and Therapeutic Resolution.
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DOI：
10.3389/fimmu.2016.00658
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发表时间：
2016
影响因子：
7.3
通讯作者：
Coles MC
中科院分区：
文献类型：
--
作者：
Butler JA;Cosgrove J;Alden K;Timmis J;Coles MC
利用小鼠基因敲除、谱系特异性报告小鼠、基因表达分析、免疫组织化学和流式细胞术的组合，对驱动次级淋巴组织形成的分子和细胞过程进行了广泛的研究。然而，由于实验模型和人类疾病病理学之间的差异，驱动三级淋巴组织（TLT）实验技术形成和功能的机制已被证明更加神秘和有争议。基于系统的方法，包括数据驱动的生物网络分析（基因相互作用网络、代谢途径网络、细胞间信号传导和级联网络）和机制建模，为理解 TLT 形成和识别可能导致组织病理学解决的机制提供了新的视角。从这个角度来看，我们通过两个案例研究来论证应用模型驱动的实验，将模拟与实验相结合，以确定驱动淋巴组织形成和功能的机制，然后讨论该实验范式的潜在应用，以确定 TLT 病理学的新治疗靶点。
The molecular and cellular processes driving the formation of secondary lymphoid tissues have been extensively studied using a combination of mouse knockouts, lineage-specific reporter mice, gene expression analysis, immunohistochemistry, and flow cytometry. However, the mechanisms driving the formation and function of tertiary lymphoid tissue (TLT) experimental techniques have proven to be more enigmatic and controversial due to differences between experimental models and human disease pathology. Systems-based approaches including data-driven biological network analysis (gene interaction network, metabolic pathway network, cell–cell signaling, and cascade networks) and mechanistic modeling afford a novel perspective from which to understand TLT formation and identify mechanisms that may lead to the resolution of tissue pathology. In this perspective, we make the case for applying model-driven experimentation using two case studies, which combined simulations with experiments to identify mechanisms driving lymphoid tissue formation and function, and then discuss potential applications of this experimental paradigm to identify novel therapeutic targets for TLT pathology.