A Tunable Diffusion-Consumption Mechanism of Cytokine Propagation Enables Plasticity in Cell-to-Cell Communication in the Immune System.
A Tunable Diffusion-Consumption Mechanism of Cytokine Propagation Enables Plasticity in Cell-to-Cell Communication in the Immune System.
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DOI：
10.1016/j.immuni.2017.03.011
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发表时间：
2017-04-18
期刊：
影响因子：
32.4
通讯作者：
Krichevsky O
中科院分区：
文献类型：
--
作者：
Oyler-Yaniv A;Oyler-Yaniv J;Whitlock BM;Liu Z;Germain RN;Huse M;Altan-Bonnet G;Krichevsky O
免疫细胞通过交换细胞因子来实现与环境相适应的反应，但这种交流发生的距离尚不清楚。在这里，我们使用体外和体内免疫反应的理论考虑和实验模型来量化致密组织中细胞因子通讯的空间范围。我们确定了细胞因子扩散和消耗之间的竞争产生了具有明显边界的高细胞因子浓度的空间生态位。这些自组装的壁龛的大小与细胞因子消耗细胞的密度成比例，这是免疫反应过程中调整的一个参数。在体内，我们测量了80-120微米长度尺度上的相互作用，这导致细胞因子暴露在细胞间的高度差异。细胞因子的这种异质分布是细胞间非遗传变异的一个来源，而这在单细胞研究中经常被忽视。因此，我们的发现为理解扩散因子在免疫反应模式中的可变性提供了基础。
Immune cells communicate by exchanging cytokines to achieve a context-appropriate response, but the distances over which such communication happens are not known. Here, we used theoretical considerations and experimental models of immune responses in vitro and in vivo to quantify the spatial extent of cytokine communications in dense tissues. We established that competition between cytokine diffusion and consumption generated spatial niches of high cytokine concentrations with sharp boundaries. The size of these self-assembled niches scaled with the density of cytokine consuming cells, a parameter that gets tuned during immune responses. In vivo, we measured interactions on length scales of 80–120 micrometers, which resulted in a high degree of cell-to-cell variance in cytokine exposure. Such heterogeneous distributions of cytokines were a source of non-genetic cell-to-cell variability that is often overlooked in single-cell studies. Our findings thus provide a basis for understanding variability in the patterning of immune responses by diffusible factors.