2. Academic Validation
  3. TSLP links intestinal nutrient sensing with amplification of the ILC2-tuft cell circuit

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

  • Nat Immunol. 2025 Dec;26(12):2218-2226. doi: 10.1038/s41590-025-02328-y.
Chang Liao 1,  Elvira Mennillo 1,  Michael G Kattah 1,  Ming Ji 2,  Zhi-En Wang 2,  Daniel J Drucker 3,  Hong-Erh Liang 1,  Richard M Locksley 4 5
Affiliations

Affiliations

  • 1 Department of Medicine, University of California, San Francisco, CA, USA.
  • 2 Howard Hughes Medical Institute, University of California, San Francisco, CA, USA.
  • 3 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
  • 4 Department of Medicine, University of California, San Francisco, CA, USA. [email protected].
  • 5 Howard Hughes Medical Institute, University of California, San Francisco, CA, USA. [email protected].
PMID: 41225178 DOI: 10.1038/s41590-025-02328-y
Abstract

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.

Figures
Products