《生命科学》 2025, 37(7): 777-786

基于正电基序的免疫受体信号转导调控机制

李　华¹ , 张雨萌² , 许琛琦^1,*

¹中国科学院分子细胞科学卓越创新中心，上海 200031 ²上海科技大学，上海 201210

摘　要：

免疫受体作为环境信号的分子传感器，在宿主防御中发挥着核心作用，其精确调控对维持免疫稳态至关重要。然而，免疫受体信号通路的异常激活或抑制可导致免疫缺陷、自身免疫病等多种病理状态，这使得靶向免疫受体的治疗策略成为生物医学研究的重要方向。值得注意的是，多种免疫受体共享一个关键的调控元件—— 碱性残基富集序列(BRS)，这一基序在信号转导中的调控机制有待深入解析。BRS 基序通常位于免疫受体的胞内近膜区，与其邻近的带电分子形成动态的静电调控网络，从多方面参与调控免疫受体信号转导。本文结合本课题组近年来的研究积累，系统性地总结了BRS 基序的免疫受体调控机制与生物学功能，并探讨了BRS 基序在工程化T 细胞治疗中的转化应用前景，为免疫治疗提供新策略。

通讯作者：许琛琦 , Email:cqxu@sibcb.ac.cn

Positively charged motif-mediated regulation of immune receptor signaling

LI Hua¹ , ZHANG Yu-Meng² , XU Chen-Qi^1,*

¹Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China ²ShanghaiTech University, Shanghai 201210, China

Abstract:

Immune receptors serve as molecular sensors of environmental signals and play central roles in host defense. Their precise regulation is critical for maintaining immune homeostasis. However, dysregulated activation or suppression of immune receptor signaling pathways can lead to various pathological conditions, including immunodeficiencies and autoimmune diseases, making immune receptor-targeted therapeutic strategies a key focus in biomedical research. Notably, various immune receptors share a critical regulatory element — the basic-residue rich sequence (BRS) motif. However, the mechanistic details of how the BRS motif modulates signal transduction remain incompletely understood. Typically localized in the cytoplasmic juxtamembrane region of immune receptors, BRS motifs interact with neighboring charged molecules to form a dynamic electrostatic regulatory network, thereby influencing immune receptor signaling through multiple mechanisms. Drawing upon our research findings in recent years, this review systematically summarizes the molecular regulatory mechanisms and biological functions of BRS motifs. Furthermore, we discuss their translational potential in engineered T-cell therapies, providing novel insights for the development of next-generation immunotherapies.

Communication Author：XU Chen-Qi , Email:cqxu@sibcb.ac.cn