法国巴黎文理研究大学Vassili Soumelis团队近期提出人类树突状细胞与辅助T细胞交流的定量多元模型。相关论文于2019年10月3日发表在《细胞》杂志上。

研究人员描述了一种整合方法，其涉及多个交流信号的蛋白质水平测量，这些信号耦合到接收细胞中的输出响应，以及数学模型以揭示输入与输出关系和信号之间的相互作用。使用人类树突状细胞（DC）与辅助T（Th）细胞交流作为模型，研究人员在428个观测值中测量了36种DC来源信号和17种Th细胞因子，这广泛涵盖Th多样性。

研究人员开发了一种数据驱动的、经过计算验证的模型，该模型捕获了56个已描述的以及290个潜在的Th细胞分化机制。通过预测背景相关的行为，研究人员证明了IL-12p70在IL-1信号传导环境中发挥Th17诱导者的新功能。

这项工作提供了独特的资源来解释控制DC与Th细胞交流的复杂组合规则，并指导其在疫苗设计和免疫疗法中的操作。

据介绍，细胞之间的交流涉及大量的分子信号，这些信号作为一种复杂语言的词汇发挥作用，其语法仍几乎是未知的。

附：英文原文

Title: A Quantitative Multivariate Model of Human Dendritic Cell-T Helper Cell Communication

Author: Maximilien Grandclaudon, Marie Perrot-Dockès, Coline Trichot, Léa Karpf, Omar Abouzid, Camille Chauvin, Philémon Sirven, Wassim Abou-Jaoudé, Frédérique Berger, Philippe Hupé, Denis Thieffry, Laure Sansonnet, Julien Chiquet, Céline Lévy-Leduc, Vassili Soumelis

Issue&Volume: 2019/10/03

Abstract: Cell-cell communication involves a large number of molecular signals that function as words of a complex language whose grammar remains mostly unknown. Here, we describe an integrative approach involving (1) protein-level measurement of multiple communication signals coupled to output responses in receiving cells and (2) mathematical modeling to uncover input-output relationships and interactions between signals. Using human dendritic cell (DC)-T helper (Th) cell communication as a model, we measured 36 DC-derived signals and 17 Th cytokines broadly covering Th diversity in 428 observations. We developed a data-driven, computationally validated model capturing 56 already described and 290 potentially novel mechanisms of Th cell specification. By predicting context-dependent behaviors, we demonstrate a new function for IL-12p70 as an inducer of Th17 in an IL-1 signaling context. This work provides a unique resource to decipher the complex combinatorial rules governing DC-Th cell communication and guide their manipulation for vaccine design and immunotherapies.

DOI: 10.1016/j.cell.2019.09.012

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31019-0