PDF(Pubmed)
Abstract：
Innate lymphoid cells (ILCs), as the innate counterpart of CD4+ T helper (Th) cells, play crucial roles in maintaining tissue homeostasis. While the ILC subsets and their corresponding Th subsets demonstrate significant similarities in core programming related to effector function and regulatory mechanisms, their principal distinctions, given their innate and adaptive lymphocyte nature, remain largely unknown. In this study, we have employed an integrative analysis of 294 bulk RNA-sequencing results across all ILC and Th subsets, using scRNA-seq algorithms. Consequently, we identify two genesets that predominantly differentiate ILCs from Th cells, as well as three genesets that distinguish various immune responses. Furthermore, through chromatin accessibility analysis, we find that the ILC geneset tends to rely on specific transcriptional regulation at promoter regions compared with the Th geneset. Additionally, we observe that ILCs and Th cells are under differential transcriptional regulation. For example, ILCs are under stronger regulation by multiple transcription factors, including RORα, GATA3, and NF-κB. Otherwise, Th cells are under stronger regulation by AP-1. Thus, our findings suggest that, despite the acknowledged similarities in effector functions between ILC subsets and corresponding Th subsets, the underlying regulatory machineries still exhibit substantial distinctions. These insights provide a comprehensive understanding of the unique roles played by each cell type during immune responses.
摘要：
固有淋巴细胞（ILC），作为CD4+辅助性T细胞（Th）的先天对应物，在维持组织稳态方面发挥关键作用。虽然ILC亚群及其相应的Th亚群在与效应子功能和调节机制相关的核心编程中表现出显著的相似性，他们的主要区别，鉴于其先天和适应性淋巴细胞的性质，基本上是未知的。在这项研究中,我们对所有ILC和Th亚群的294个批量RNA测序结果进行了综合分析，使用scRNA-seq算法。因此,我们确定了两个主要区分Th细胞ILC的基因组，以及区分各种免疫反应的三个基因组。此外，通过染色质可及性分析，我们发现，与Th基因组相比，ILC基因组倾向于依赖于启动子区域的特异性转录调控。此外,我们观察到ILC和Th细胞处于差异转录调控之下。例如,ILC受到多种转录因子的更强调节，包括RORα,GATA3和NF-κB。否则,Th细胞受到AP-1更强的调节。因此，我们的研究结果表明，尽管公认的ILC子集和相应的Th子集之间的效应子功能相似，基本的监管机构仍然表现出很大的区别。这些见解提供了对每种细胞类型在免疫应答过程中发挥的独特作用的全面理解。
