The role of the tuft cell–interleukin-25 axis in the pathogenesis of inflammatory bowel disease

作者：Zishao Tao, Li Li, Ying Zhang, Yufang Tang, Simeng Zhang, Heying Yang, Guorong Jiang, Rui Zhang, Zhiwei Wu, Miao He · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1629060 · 被引用次数：8 · 研究领域：IL-33, ST2, and ILC Pathways、Eosinophilic Esophagitis、Immune Cell Function and Interaction

Emerging evidence highlights the tuft cell—Interleukin-25 (IL-25) axis (tuft/IL-25 axis) as a critical orchestrator bridging luminal stimuli and intestinal immunity in Inflammatory Bowel Disease (IBD), which encompasses Crohn’s Disease (CD) and Ulcerative Colitis (UC). This review synergises current understanding of how dysregulation within this axis contributes to IBD pathogenesis, arising from disrupted immune homeostasis involving aberrant microbiota responses, genetic susceptibility, and immune pathway dysregulation. Central to this axis, intestinal tuft cells act as chemosensory epithelial sentinels, differentiating in response to microbial and metabolic cues to become the primary source of IL-25. IL-25, signaling via IL-17RB, engages innate and adaptive immune cells, particularly group 2 innate lymphoid cells (ILC2s). While IL-33-responsive homeostatic ILC2s (nILC2s) promote mucosal repair, IL-25-driven inflammatory ILC2s (iILC2s) amplify inflammation, positioning them as pivotal effectors. Critically, IL-25 exhibits a context-dependent “double-edged” role: engagement with IL-25R + T cells and modulation of downstream signaling can exert anti-inflammatory effects and enhance barrier integrity, yet dysregulation drives pro-inflammatory injury. The axis is dynamically regulated by diverse luminal factors: helminth infection activates the tuft-ILC2 circuit, inducing protective type 2 immunity; specific microbial metabolites (e.g., succinate, SCFAs) modulate its activity; a...