Charge-based immunoreceptor signalling in health and disease

IF 67.7 1区 医学 Q1 IMMUNOLOGY
Xiaoshan Shi, Xing He, Chenqi Xu
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引用次数: 0

Abstract

Immunoreceptors have crucial roles in sensing environmental signals and initiating immune responses to protect the host. Dysregulation of immunoreceptor signalling can therefore lead to a range of diseases, making immunoreceptor-based therapies a promising frontier in biomedicine. A common feature of various immunoreceptors is the basic-residue-rich sequence (BRS), which is a largely unexplored aspect of immunoreceptor signalling. The BRS is typically located in the cytoplasmic juxtamembrane region of immunoreceptors, where it forms dynamic interactions with neighbouring charged molecules to regulate signalling. Loss or gain of the basic residues in an immunoreceptor BRS has been linked to severe human diseases, such as immunodeficiency and autoimmunity. In this Perspective, we describe the role of BRSs in various immunoreceptors, elucidating their signalling mechanisms and biological functions. Furthermore, we highlight pathogenic mutations in immunoreceptor BRSs and discuss the potential of leveraging BRS signalling in engineered T cell-based therapies. The basic-residue-rich sequence (BRS) is a common motif located in the cytoplasmic tail of most immunoreceptors. This Perspective highlights the mechanisms of BRS signalling, its pathophysiological importance and how to harness BRS signalling to develop next-generation immunotherapy.

Abstract Image

Abstract Image

健康和疾病中基于电荷的免疫受体信号传递
免疫感受器在感知环境信号和启动免疫反应以保护宿主方面发挥着至关重要的作用。因此,免疫受体信号的失调可导致一系列疾病,从而使基于免疫受体的疗法成为生物医学中前景广阔的前沿领域。各种免疫受体的一个共同特征是富含基本氨基酸的序列(BRS),这在很大程度上是免疫受体信号传导中一个尚未探索的方面。富含碱基残基的序列通常位于免疫受体的胞浆并膜区,它与邻近的带电分子形成动态相互作用,从而调节信号传导。免疫受体 BRS 基本残基的缺失或增益与免疫缺陷和自身免疫等严重人类疾病有关。在本《视角》中,我们描述了 BRS 在各种免疫受体中的作用,阐明了它们的信号机制和生物功能。此外,我们还强调了免疫受体 BRS 的致病突变,并讨论了在基于 T 细胞的工程疗法中利用 BRS 信号的潜力。
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来源期刊
Nature Reviews Immunology
Nature Reviews Immunology 医学-免疫学
CiteScore
93.40
自引率
0.40%
发文量
131
审稿时长
6-12 weeks
期刊介绍: Nature Reviews Immunology is a journal that provides comprehensive coverage of all areas of immunology, including fundamental mechanisms and applied aspects. It has two international standard serial numbers (ISSN): 1474-1733 for print and 1474-1741 for online. In addition to review articles, the journal also features recent developments and new primary papers in the field, as well as reflections on influential people, papers, and events in the development of immunology. The subjects covered by Nature Reviews Immunology include allergy and asthma, autoimmunity, antigen processing and presentation, apoptosis and cell death, chemokines and chemokine receptors, cytokines and cytokine receptors, development and function of cells of the immune system, haematopoiesis, infection and immunity, immunotherapy, innate immunity, mucosal immunology and the microbiota, regulation of the immune response, signalling in the immune system, transplantation, tumour immunology and immunotherapy, and vaccine development.
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