Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan.
IUBMB Life. 2013 Jan;65(1):28-34. doi: 10.1002/iub.1110.
The immune system is a very complex and dynamic cellular system, and its intricacies are considered akin to those of human society. Disturbance of homeostasis of the immune system results in various types of diseases; therefore, the homeostatic mechanism of the immune system has long been a subject of great interest in biology, and a lot of information has been accumulated at the cellular and the molecular levels. However, the sociological aspects of the immune system remain too abstract to address because of its high complexity, which mainly originates from a large number and variety of cell-cell interactions. As long-range interactions mediated by cytokines play a key role in the homeostasis of the immune system, cytokine secretion analyses, ranging from analyses of the micro level of individual cells to the macro level of a bulk of cell ensembles, provide us with a solid basis of a sociological viewpoint of the immune system. In this review, as the first step toward a comprehensive understanding of immune cell sociology, cytokine secretion of immune cells is surveyed with a special emphasis on the single-cell level, which has been overlooked but should serve as a basis of immune cell sociology. Now that it has become evident that large cell-to-cell variations in cytokine secretion exist at the single-cell level, we face a tricky yet interesting question: How is homeostasis maintained when the system is composed of intrinsically noisy agents? In this context, we discuss how the heterogeneity of cytokine secretion at the single-cell level affects our view of immune cell sociology. While the apparent inconsistency between homeostasis and cell-to-cell heterogeneity is difficult to address by a conventional reductive approach, comparison and integration of single-cell data with macroscopic data will offer us a new direction for the comprehensive understanding of immune cell sociology.
免疫系统是一个非常复杂和动态的细胞系统，其复杂性被认为类似于人类社会的复杂性。免疫系统的动态平衡被打破会导致各种类型的疾病；因此，免疫系统的动态平衡机制一直是生物学中非常感兴趣的课题，在细胞和分子水平上已经积累了大量的信息。然而，由于其高度复杂性，免疫系统的社会学方面仍然过于抽象而无法解决，主要源于大量的细胞间相互作用和多种细胞间相互作用。由于细胞因子介导的长程相互作用在免疫系统的动态平衡中起着关键作用，因此对细胞因子分泌的分析，从单个细胞的微观水平到大量细胞集合体的宏观水平，为我们提供了免疫系统社会学观点的坚实基础。在这篇综述中，作为全面理解免疫细胞社会学的第一步，我们特别关注了单细胞水平上的免疫细胞细胞因子分泌，这一点一直被忽视，但应该作为免疫细胞社会学的基础。既然已经明显到细胞因子分泌在单细胞水平上存在着很大的细胞间变化，我们就面临着一个棘手但又很有趣的问题：当系统由固有噪声的细胞组成时，如何维持动态平衡？在这种情况下，我们讨论了单细胞水平上细胞因子分泌的异质性如何影响我们对免疫细胞社会学的看法。虽然稳态和细胞间异质性之间的明显不一致性很难通过传统的还原方法来解决，但单细胞数据与宏观数据的比较和整合将为我们全面理解免疫细胞社会学提供一个新的方向。
