Secretogranin 2 Binds LILRB4 Resulting in Immunosuppression

Authors

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

Language

English

Publication Date

9-1-2025

Journal

Nature Immunology

DOI

10.1038/s41590-025-02233-4

PMID

40707822

PMCID

PMC12414541

PubMedCentral® Posted Date

1-24-2026

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Animals, Receptors, Immunologic, Mice, Humans, Immune Tolerance, Mice, Transgenic, Secretogranin II, Signal Transduction, Monocytes, Mice, Knockout, Membrane Glycoproteins, Protein Binding, Mice, Inbred C57BL, Cell Line, Tumor, T-Lymphocytes

Published Open-Access

yes

Recommended Citation

Yang, Xing; Huang, Ryan; Fang, Meng; et al., "Secretogranin 2 Binds LILRB4 Resulting in Immunosuppression" (2025). Faculty, Staff and Student Publications. 4994.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4994