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<p>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 <i>LILRB4</i> 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.</p>

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Secretogranin 2 binds LILRB4 resulting in immunosuppression

  • 期刊论文

  • 发表日期：

    2025年7月24日

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  • 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

摘要

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.