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<p>In inflammatory bowel disease (IBD), complex immune dysregulation induces chronic inflammation. TREM1 is a receptor expressed on myeloid cells and is activated by ligands such as PGLYRP1 to amplify inflammatory responses. Here, we analyze the function of TREM1 signaling in neutrophil-driven inflammation, identifying two positive feedback loops. First, neutrophils activated by phorbol 12-myristate 13-acetate (PMA) or by bacteria release PGLYRP1, which forms a ligand complex with bacterial peptidoglycan and activates TREM1, thereby enhancing neutrophil degranulation, reactive oxygen species production, and NETosis. Second, TREM1 activation on monocytes promotes the secretion of chemokines and cytokines that recruit and activate additional neutrophils, further perpetuating inflammation. In vivo, TREM1 activation exacerbates colitis in mice, with the gut commensal bacterium <i>Blautia faecis</i> potentially contributing to human TREM1 activation in IBD. In biopsy samples from patients with IBD, an elevated TREM1 pathway signature is associated with inflamed tissue and treatment resistance in ulcerative colitis. Our findings thus highlight TREM1 as a regulator of mucosal inflammation, and a potential therapeutic target for IBD.</p>

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TREM1 signaling amplifies neutrophil-mediated inflammation in inflammatory bowel disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月8日

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  • Warrison Andrade,
  • Hao Xu,
  • Yutian Peng,
  • Zhiyuan Yao,
  • Jack Bevers,
  • Rhyan Puno,
  • Yongchang Shi,
  • Victoria Pham,
  • Meena Choi,
  • Yonglian Sun,
  • Alexis Scherl,
  • Ruoyu Zhang,
  • Alexandra Paun,
  • Tao Sun,
  • Yuxin Liang,
  • Nandhini Ramamoorthi,
  • Jianyong Wang,
  • Dhaya Seshasayee,
  • Gerald Nakamura,
  • Man-Wah Tan,
  • Hua Zhang,
  • Mary Keir,
  • Jason Hackney,
  • Saiyu Hang

摘要

In inflammatory bowel disease (IBD), complex immune dysregulation induces chronic inflammation. TREM1 is a receptor expressed on myeloid cells and is activated by ligands such as PGLYRP1 to amplify inflammatory responses. Here, we analyze the function of TREM1 signaling in neutrophil-driven inflammation, identifying two positive feedback loops. First, neutrophils activated by phorbol 12-myristate 13-acetate (PMA) or by bacteria release PGLYRP1, which forms a ligand complex with bacterial peptidoglycan and activates TREM1, thereby enhancing neutrophil degranulation, reactive oxygen species production, and NETosis. Second, TREM1 activation on monocytes promotes the secretion of chemokines and cytokines that recruit and activate additional neutrophils, further perpetuating inflammation. In vivo, TREM1 activation exacerbates colitis in mice, with the gut commensal bacterium Blautia faecis potentially contributing to human TREM1 activation in IBD. In biopsy samples from patients with IBD, an elevated TREM1 pathway signature is associated with inflamed tissue and treatment resistance in ulcerative colitis. Our findings thus highlight TREM1 as a regulator of mucosal inflammation, and a potential therapeutic target for IBD.