Sciumè Giuseppe, Shih Han-Yu, Mikami Yohei, O'Shea John J
Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.
Lymphocyte and Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, United States.
Front Immunol. 2017 Nov 13;8:1579. doi: 10.3389/fimmu.2017.01579. eCollection 2017.
The discovery of innate lymphoid cells (ILCs) with selective production of cytokines typically attributed to subsets of T helper cells forces immunologists to reassess the mechanisms by which selective effector functions arise. The parallelism between ILCs and T cells extends beyond these two cell types and comprises other innate-like T lymphocytes. Beyond the recognition of specialized effector functionalities in diverse lymphocytes, features typical of T cells, such as plasticity and memory, are also relevant for innate lymphocytes. Herein, we review what we have learned in terms of the molecular mechanisms underlying these shared functions, focusing on insights provided by next generation sequencing technologies. We review data on the role of lineage-defining- and signal-dependent transcription factors (TFs). ILC regulomes emerge developmentally whereas the much of the open chromatin regions of T cells are generated acutely, in an activation-dependent manner. And yet, these regions of open chromatin in T cells and ILCs have remarkable overlaps, suggesting that though accessibility is acquired by distinct modes, the end result is that convergent signaling pathways may be involved. Although much is left to be learned, substantial progress has been made in understanding how TFs and epigenomic status contribute to ILC biology in terms of differentiation, specification, and plasticity.
天然淋巴细胞(ILC)能够选择性产生通常归因于辅助性T细胞亚群的细胞因子,这一发现促使免疫学家重新评估选择性效应功能产生的机制。ILC与T细胞之间的相似性不仅限于这两种细胞类型,还包括其他固有样T淋巴细胞。除了认识到不同淋巴细胞具有特殊的效应功能外,T细胞的典型特征,如可塑性和记忆性,也与固有淋巴细胞相关。在此,我们回顾了我们在这些共享功能的分子机制方面所学到的知识,重点关注下一代测序技术提供的见解。我们回顾了谱系定义和信号依赖转录因子(TF)作用的数据。ILC的调控组是在发育过程中出现的,而T细胞的许多开放染色质区域是以激活依赖的方式急性产生的。然而,T细胞和ILC中的这些开放染色质区域有显著重叠,这表明尽管可及性是通过不同方式获得的,但最终结果可能涉及趋同的信号通路。尽管仍有许多有待了解,但在理解TF和表观基因组状态如何在分化、特化和可塑性方面对ILC生物学产生影响方面已经取得了实质性进展。