Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA; Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
Trends Immunol. 2023 Dec;44(12):965-970. doi: 10.1016/j.it.2023.10.009. Epub 2023 Nov 9.
A binary classification of macrophage activation as inflammatory or resolving does not capture the diversity of macrophage states observed in tissues. However, framing macrophage activation as a continuous spectrum of states overlooks the intracellular and extracellular networks that regulate and coordinate macrophage responses. Here, we suggest that the systems biology concept of network motifs, which incorporate rules of local molecular interactions, is useful for reframing macrophage activation. Because network motifs can be used to regulate distinct biological functions, they offer a simplified unit that can be compared across organismal, tissue, and disease contexts. Moreover, defining macrophage states as combinations of functional modules regulated by network motifs offers a framework to ultimately predict and target macrophage responses arising in complex environments.
巨噬细胞激活的二分法，即促炎或修复型，无法捕捉到组织中观察到的巨噬细胞状态的多样性。然而，将巨噬细胞激活框定为一个连续的状态谱，忽略了调节和协调巨噬细胞反应的细胞内和细胞外网络。在这里，我们认为网络基元的系统生物学概念，即包含局部分子相互作用规则的网络基元，对于重新构建巨噬细胞激活是有用的。由于网络基元可用于调节不同的生物学功能，因此它们提供了一个简化的单元，可以在生物体、组织和疾病背景下进行比较。此外，将巨噬细胞状态定义为受网络基元调节的功能模块的组合，为预测和靶向复杂环境中产生的巨噬细胞反应提供了一个框架。
