德克萨斯大学研究团队的一项最新研究报道了分泌颗粒蛋白2与LILRB4结合导致免疫抑制。相关论文于2025年7月24日发表在《自然—免疫学》杂志上。

在这里，该课题组发现分泌颗粒蛋白2 (SCG2)，一个颗粒蛋白家族成员，在单核细胞上与白细胞免疫球蛋白样受体B4 （LILRB4）功能相互作用。肿瘤来源的SCG2以T细胞依赖的方式促进骨髓特异性LILRB4转基因小鼠的肿瘤生长，而宿主小鼠中SCG2缺乏会损害肿瘤进展并减少免疫抑制性单核细胞的浸润。阻断LILRB4可消除scg2诱导的信号、免疫抑制和肿瘤生长。从机制上讲，SCG2-LILRB4相互作用触发SHP募集和与SHP无关的STAT3激活。这些发现确定了SCG2在调节单核细胞免疫抑制中的功能，并提示SCG2 -LILRB4轴可能是一个治疗靶点。

据了解，免疫抑制性骨髓细胞在多种生理和病理环境中都很重要，包括肿瘤的发展，但激素如何调节其活性尚不清楚。分泌颗粒蛋白（Secretogranins）是内分泌细胞和神经细胞中的一类分泌蛋白，被认为具有激素原或激素的功能，但其特异性受体尚不清楚。

附：英文原文

Title: Secretogranin 2 binds LILRB4 resulting in immunosuppression

Author: Yang, Xing, Huang, Ryan, Fang, Meng, He, Yubo, Xie, Jingjing, Liu, Xiaoye, Zhang, Chengcheng, Lou, Qi, Deng, Mi, Xiong, Wei, Lewis, Cheryl, Sadek, Zade, Gupta, Ankit, Chen, Lianqi, Zhang, Xuewu, Guo, Lei, Xu, Lin, Zhang, Ningyan, An, Zhiqiang, Zhang, Cheng Cheng

Issue&Volume: 2025-07-24

Abstract: Immunosuppressive myeloid cells are important in a variety of physiological and pathological contexts, including tumor development, but how hormones might regulate their activity is unclear. Secretogranins, a family of secretory proteins in endocrine and neuronal cells, are proposed to function as prohormones or hormones, but their specific receptors are unknown. Here we show that secretogranin 2 (SCG2), a granin family member, functionally interacts with leukocyte immunoglobulin-like receptor B4 (LILRB4) on monocytic cells. Tumor-derived SCG2 promotes tumor growth in myeloid-specific LILRB4 transgenic mice in a T cell-dependent manner, whereas SCG2 deficiency in host mice impairs tumor progression and reduces infiltration of immunosuppressive monocytic cells. Blockade of LILRB4 abrogates SCG2-induced signaling, immunosuppression and tumor growth. Mechanistically, this SCG2–LILRB4 interaction triggers SHP recruitment and SHP-independent STAT3 activation. These findings define a function for SCG2 in regulating monocytic immunosuppression and suggest that the SCG2–LILRB4 axis might be a therapeutic target.

DOI: 10.1038/s41590-025-02233-4

Source: https://www.nature.com/articles/s41590-025-02233-4