{"title":"Charge-based immunoreceptor signalling in health and disease","authors":"Xiaoshan Shi, Xing He, Chenqi Xu","doi":"10.1038/s41577-024-01105-6","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7000,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41577-024-01105-6","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
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.