Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease
Abstract The immunological synapse (IS) serves as the fundamental architectural framework for direct interactions and secretory crosstalk between immune cells, as well as between immune cells and other cells. Its dysregulation is thought to be a key underlying cause of immune evasion or inflammation...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-08-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02332-6 |
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| author | Zheng Chao Qi Mei Chunguang Yang Jing Luo Peikun Liu Hao Peng Xiangdong Guo Zhinan Yin Le Li Zhihua Wang |
| author_facet | Zheng Chao Qi Mei Chunguang Yang Jing Luo Peikun Liu Hao Peng Xiangdong Guo Zhinan Yin Le Li Zhihua Wang |
| author_sort | Zheng Chao |
| collection | DOAJ |
| description | Abstract The immunological synapse (IS) serves as the fundamental architectural framework for direct interactions and secretory crosstalk between immune cells, as well as between immune cells and other cells. Its dysregulation is thought to be a key underlying cause of immune evasion or inflammation observed in various diseases, including tumors and infections. Numerous recent studies have addressed key signaling mechanisms and reported novel targets related to IS, further broadening our understanding of its function and regulatory factors. However, a comprehensive review that highlights recent progress and consolidates past knowledge is still lacking. In this study, we delineated the pre- and postsynaptic structures constituting the IS between T cells, natural killer (NK) cells, dendritic cells (DCs), and macrophages. We also detail the specific signaling mechanisms and pathways that modulate the formation and disassembly of the IS, including cytoskeletal remodeling, membrane reshaping, integrin signaling, and force transduction. Following these experimental findings, we systematically review the central roles of IS in maintaining homeostasis and health and outline various diseases arising from IS disorders. Finally, we thoroughly explore targets and treatments related to IS on the basis of preclinical evidence and clinical trials, with the aim of providing further investigatory and therapeutic insights for researchers and clinicians. |
| format | Article |
| id | doaj-art-b75460a353ec4fdab4e7a2cde6c0d99f |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-b75460a353ec4fdab4e7a2cde6c0d99f2025-08-20T03:41:57ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-08-0110113610.1038/s41392-025-02332-6Immunological synapse: structures, molecular mechanisms and therapeutic implications in diseaseZheng Chao0Qi Mei1Chunguang Yang2Jing Luo3Peikun Liu4Hao Peng5Xiangdong Guo6Zhinan Yin7Le Li8Zhihua Wang9Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical UniversityDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyThe Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract The immunological synapse (IS) serves as the fundamental architectural framework for direct interactions and secretory crosstalk between immune cells, as well as between immune cells and other cells. Its dysregulation is thought to be a key underlying cause of immune evasion or inflammation observed in various diseases, including tumors and infections. Numerous recent studies have addressed key signaling mechanisms and reported novel targets related to IS, further broadening our understanding of its function and regulatory factors. However, a comprehensive review that highlights recent progress and consolidates past knowledge is still lacking. In this study, we delineated the pre- and postsynaptic structures constituting the IS between T cells, natural killer (NK) cells, dendritic cells (DCs), and macrophages. We also detail the specific signaling mechanisms and pathways that modulate the formation and disassembly of the IS, including cytoskeletal remodeling, membrane reshaping, integrin signaling, and force transduction. Following these experimental findings, we systematically review the central roles of IS in maintaining homeostasis and health and outline various diseases arising from IS disorders. Finally, we thoroughly explore targets and treatments related to IS on the basis of preclinical evidence and clinical trials, with the aim of providing further investigatory and therapeutic insights for researchers and clinicians.https://doi.org/10.1038/s41392-025-02332-6 |
| spellingShingle | Zheng Chao Qi Mei Chunguang Yang Jing Luo Peikun Liu Hao Peng Xiangdong Guo Zhinan Yin Le Li Zhihua Wang Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease Signal Transduction and Targeted Therapy |
| title | Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease |
| title_full | Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease |
| title_fullStr | Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease |
| title_full_unstemmed | Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease |
| title_short | Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease |
| title_sort | immunological synapse structures molecular mechanisms and therapeutic implications in disease |
| url | https://doi.org/10.1038/s41392-025-02332-6 |
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