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bioRxiv · 10.1101/2024.10.14.618111

Telocytes link epithelial nutrient sensing with amplification of the ILC2-tuft cell circuit

Liao, C.·Ji, M.·Wang, Z.-E.·Drucker, D. J.·Liang, H.-E.·Locksley, R. M.
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Abstract

Group 2 innate lymphocytes (ILC2s) are prevalent in small intestine but engagement of type 2 immunity during basal processes are incompletely described. Thymic stromal lymphopoietin (TSLP), a cytokine implicated in ILC2 activation, was constitutively expressed in villus telocytes and crypt-associated trophocytes, specialized fibroblasts that sustain epithelial identity. Feeding increased TSLP and induced ILC2 type 2 cytokines that were attenuated by deletion of TSLP in PDGFR+ stromal cells or TSLP receptor on ILC2s. Mouse and human telocytes expressed receptors for glucagon-like peptide-2 (GLP-2), which is released by enteroendocrine cells (EECs) after eating. GLP-2 induced intestinal TSLP, TSLP-dependent ILC2 cytokine production, and tuft cell hyperplasia. The telocyte-alarmin relay couples EEC nutrient detection with amplification of a tuft cell chemosensory circuit that diversifies surveillance of ingested cargo. One-Sentence SummaryIntestinal telocyte TSLP relays signals from enteroendocrine cells to ILC2s to amplify the tuft cell circuit in response to feeding.

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Liao, C., Ji, M., Wang, Z.-E., Drucker, D. J., Liang, H.-E., Locksley, R. M.. 2024-10-17. Telocytes link epithelial nutrient sensing with amplification of the ILC2-tuft cell circuit. https://doi.org/10.1101/2024.10.14.618111

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