Pulendran Bali
Emory Vaccine Center and Department of Pathology, Emory University, Atlanta, GA 30329, USA.
J Immunol. 2005 Mar 1;174(5):2457-65. doi: 10.4049/jimmunol.174.5.2457.
One of the most fundamental questions in biology is: "How do cells differentiate in the right place, at the right time, into the right kinds?" Understanding the phenomenon of cell differentiation in its spatial and temporal framework is a prelude to understanding the development and physiology of all multicellular systems, including the immune system. Insights over the past 2300 years, since Aristotle, suggest that biological differentiation is guided by the interplay between genetic programs and specific environmental signals. This is exemplified by the mammalian immune response to pathogens, where qualitatively different types can emerge. Although it is appreciated that this type immunity is critical for optimal defense against different pathogens, the early "decision-making mechanisms" are largely obscure. Recent developments in innate immunity and genomics, especially in the biology of dendritic cells (DCs) and pathogen recognition receptors, have stimulated intense research in understanding the mechanisms guiding the differentiation of Th1, Th2, and T regulatory responses. In this study, I summarize recent findings which suggest that activation of DCs via distinct pathogen recognition receptors stimulate different gene expression programs and signaling networks in DCs that guide the variegation of immune responses.
“细胞如何在正确的位置、正确的时间分化为正确的类型？”在时空框架内理解细胞分化现象是理解包括免疫系统在内的所有多细胞系统发育和生理学的前奏。自亚里士多德以来的2300多年里，各种见解表明，生物分化是由基因程序和特定环境信号之间的相互作用引导的。哺乳动物对病原体的免疫反应就是一个例证，其中会出现性质不同的类型。尽管人们认识到这种类型的免疫对于最佳抵御不同病原体至关重要，但早期的“决策机制”在很大程度上仍不清楚。固有免疫和基因组学的最新进展，尤其是树突状细胞（DCs）生物学和病原体识别受体方面的进展，激发了人们对理解引导Th1、Th2和T调节反应分化机制的深入研究。在本研究中，我总结了最近的发现，这些发现表明，通过不同的病原体识别受体激活DCs会刺激DCs中不同的基因表达程序和信号网络，从而引导免疫反应的多样化。
