美国霍华德休斯医学研究所Alexander Y. Rudensky和Chrysothemis C. Brown等研究人员合作揭示了小鼠和人类树突状细胞（DC）异质性的转录基础。这一研究成果10月24日在线发表于国际学术期刊《细胞》。

通过将转录和染色质分析与遗传报告基因表达相结合，研究人员确定了两个主要的cDC2谱系，其由不同的发育途径和转录调节因子定义，包括T-bet和RORγt，这是两个已知的定义固有和适应性淋巴细胞亚群的关键转录因子。这些新颖的cDC2谱系拥有独特的代谢和功能特征。这些发现进一步揭示了人类中保守的DC异质性以及新定义的cDC2亚群在人类癌症中的存在。

据了解，DC在协调适应性免疫反应中起着至关重要的作用，因为它们具有启动T细胞反应并将其分化为效应谱系的独特能力。基于表型标记及其对CD8和CD4 T细胞的启动能力，经典DC已分为cDC1和cDC2两个亚群。虽然先前的研究已经很好地描述了cDC1亚群的转录调控，但对cDC2的发育和功能仍然知之甚少。

附：英文原文

Title: Transcriptional Basis of Mouse and Human Dendritic Cell Heterogeneity

Author: Chrysothemis C. Brown, Herman Gudjonson, Yuri Pritykin, Deeksha Deep, Vincent-Philippe Lavallée, Alejandra Mendoza, Rachel Fromme, Linas Mazutis, Charlotte Ariyan, Christina Leslie, Dana Pe’er, Alexander Y. Rudensky

Issue&Volume: 2019/10/24

Abstract: Dendritic cells (DCs) play a critical role in orchestrating adaptive immune responses due to their unique ability to initiate T cell responses and direct their differentiation into effector lineages. Classical DCs have been divided into two subsets, cDC1 and cDC2, based on phenotypic markers and their distinct abilities to prime CD8 and CD4 T cells. While the transcriptional regulation of the cDC1 subset has been well characterized, cDC2 development and function remain poorly understood. By combining transcriptional and chromatin analyses with genetic reporter expression, we identified two principal cDC2 lineages defined by distinct developmental pathways and transcriptional regulators, including T-bet and RORγt, two key transcription factors known to define innate and adaptive lymphocyte subsets. These novel cDC2 lineages were characterized by distinct metabolic and functional programs. Extending our findings to humans revealed conserved DC heterogeneity and the presence of the newly defined cDC2 subsets in human cancer.

DOI: 10.1016/j.cell.2019.09.035

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31116-X