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<p>Group 2 innate lymphocytes (ILC2s) are prevalent in small intestine but their role during homeostasis is unclear. Here we show that thymic stromal lymphopoietin (TSLP)—a cytokine implicated in ILC2 activation—is expressed constitutively in subepithelial fibroblasts, including telocytes and crypt-associated trophocytes, which are specialized fibroblasts necessary to sustain epithelial identity. Feeding increases TSLP and induces ILC2 type 2 cytokines that are attenuated by deletion of TSLP in fibroblasts or TSLP receptor on ILC2s. Both mouse and human intestinal fibroblasts express receptors for glucagon-like peptide-2 (GLP-2)—an intestinotrophic growth factor released by enteroendocrine cells following food intake. GLP-2 promotes intestinal TSLP in mouse and human intestinal fibroblasts, and TSLP-dependent ILC2 activation and tuft cell hyperplasia in mice, thus linking nutrient detection with ILC2-mediated amplification of the tuft cell chemosensory circuit that promotes epithelial surveillance of ingested cargo.</p>

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TSLP links intestinal nutrient sensing with amplification of the ILC2–tuft cell circuit

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月12日

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  • Chang Liao,
  • Elvira Mennillo,
  • Michael G. Kattah,
  • Ming Ji,
  • Zhi-En Wang,
  • Daniel J. Drucker,
  • Hong-Erh Liang,
  • Richard M. Locksley

摘要

Group 2 innate lymphocytes (ILC2s) are prevalent in small intestine but their role during homeostasis is unclear. Here we show that thymic stromal lymphopoietin (TSLP)—a cytokine implicated in ILC2 activation—is expressed constitutively in subepithelial fibroblasts, including telocytes and crypt-associated trophocytes, which are specialized fibroblasts necessary to sustain epithelial identity. Feeding increases TSLP and induces ILC2 type 2 cytokines that are attenuated by deletion of TSLP in fibroblasts or TSLP receptor on ILC2s. Both mouse and human intestinal fibroblasts express receptors for glucagon-like peptide-2 (GLP-2)—an intestinotrophic growth factor released by enteroendocrine cells following food intake. GLP-2 promotes intestinal TSLP in mouse and human intestinal fibroblasts, and TSLP-dependent ILC2 activation and tuft cell hyperplasia in mice, thus linking nutrient detection with ILC2-mediated amplification of the tuft cell chemosensory circuit that promotes epithelial surveillance of ingested cargo.