Review Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease, 2025, Chao et al.

[SNT Gatchaman]

Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease

Spoiler: Authors

Chao, Zheng; Mei, Qi; Yang, Chunguang; Luo, Jing; Liu, Peikun; Peng, Hao; Guo, Xiangdong; Yin, Zhinan; Li, Le; Wang, Zhihua

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.

Web | DOI | PDF | Nature Signal Transduction and Targeted Therapy | Open Access

 

[SNT Gatchaman]

I'm posting this paper in its own thread, responding to a summary point in the year-in-review thread.

2) The biggest piece of the puzzle comes from DecodeME and the genetics study by Mark Snyder’s team at Stanford. Both pointed to the brain and neuronal communication.

Are DecodeME findings solely pointing to brain? I know the Magma evaluation indicated brain tissue enrichment for these genes, but synapse-related genes could also be playing a role in the immune system as well as the neurological system.

Immune cells within the body are constantly exchanging information to regulate the immune system and maintain the health of the organism. At the heart of these dynamic interactions lies the IS, a structural foundation analogous to its neuronal counterpart. Research on the IS has historically focused on its composition and regulatory mechanisms due to the complexity of its formation, the numerous signaling pathways involved, and the intricate molecular events at the synaptic interface. This has only recently led to a preliminary comprehensive understanding of the IS.

Currently, it is considered an essential checkpoint for various immune responses, widely controlling immune surveillance and host defense against tumors and pathogenic substances, coordinating the magnitude and scope of immune reactions, and even mediating immune tolerance while assisting in neural development.

Unexpectedly, researchers have observed IS dysfunction in many diseases, prompting investigations into the specific connections between IS dysfunction and various conditions