Regulation of the tuft cell-ILC2 circuit in intestinal mucosal immunity

The intestinal mucosal immune system maintains homeostasis through complex interactions between epithelial cells and innate lymphoid cells in the lamina propria. Tuft cells, previously overlooked intestinal epithelial cell types, detect parasites and metabolites via Sucnr1 and TAS2R receptors. They...

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Main Authors: Kaiyu Shang, Xinxin Qi, Tingting Tian, Huidong Shi, Yuejie Zhu, Fengbo Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568062/full
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author Kaiyu Shang
Xinxin Qi
Tingting Tian
Huidong Shi
Yuejie Zhu
Fengbo Zhang
author_facet Kaiyu Shang
Xinxin Qi
Tingting Tian
Huidong Shi
Yuejie Zhu
Fengbo Zhang
author_sort Kaiyu Shang
collection DOAJ
description The intestinal mucosal immune system maintains homeostasis through complex interactions between epithelial cells and innate lymphoid cells in the lamina propria. Tuft cells, previously overlooked intestinal epithelial cell types, detect parasites and metabolites via Sucnr1 and TAS2R receptors. They secrete IL-25, which activates type 2 innate lymphoid cell (ILC2) via the IL-25R receptor. ILC2 releases IL-13, resulting in further promotion of tuft and goblet cells from stem cells. This positive feedback loop amplifies the local type 2 immune response, combating parasitic infections. Tuft cells also recognize viruses and bacteria, but the role played by the tuft cell-ILC2 circuit in this process is not yet clear. Furthermore, tuft cell-ILC2 circuit is influenced by dietary fiber, intestinal microbiota, and other factors, contributing to new functions in maintaining intestinal homeostasis. In inflammatory bowel disease, this immunological circuit may be protective. This review summarizes the current understanding of the tuft cell-ILC2 circuit, its regulatory mechanisms, and potential implications in intestinal disease. Graphical abstract (by Figdraw 2.0)
format Article
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issn 1664-3224
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publishDate 2025-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-cbd19d1efd09494f944d7337fa49ec662025-08-20T02:22:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15680621568062Regulation of the tuft cell-ILC2 circuit in intestinal mucosal immunityKaiyu Shang0Xinxin Qi1Tingting Tian2Huidong Shi3Yuejie Zhu4Fengbo Zhang5Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaReproductive Medicine Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaThe intestinal mucosal immune system maintains homeostasis through complex interactions between epithelial cells and innate lymphoid cells in the lamina propria. Tuft cells, previously overlooked intestinal epithelial cell types, detect parasites and metabolites via Sucnr1 and TAS2R receptors. They secrete IL-25, which activates type 2 innate lymphoid cell (ILC2) via the IL-25R receptor. ILC2 releases IL-13, resulting in further promotion of tuft and goblet cells from stem cells. This positive feedback loop amplifies the local type 2 immune response, combating parasitic infections. Tuft cells also recognize viruses and bacteria, but the role played by the tuft cell-ILC2 circuit in this process is not yet clear. Furthermore, tuft cell-ILC2 circuit is influenced by dietary fiber, intestinal microbiota, and other factors, contributing to new functions in maintaining intestinal homeostasis. In inflammatory bowel disease, this immunological circuit may be protective. This review summarizes the current understanding of the tuft cell-ILC2 circuit, its regulatory mechanisms, and potential implications in intestinal disease. Graphical abstract (by Figdraw 2.0)https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568062/fulltuft cellsmucosal immunityintestinal homeostasisinflammatory bowel diseasetuft cell-ILC2 circuit
spellingShingle Kaiyu Shang
Xinxin Qi
Tingting Tian
Huidong Shi
Yuejie Zhu
Fengbo Zhang
Regulation of the tuft cell-ILC2 circuit in intestinal mucosal immunity
Frontiers in Immunology
tuft cells
mucosal immunity
intestinal homeostasis
inflammatory bowel disease
tuft cell-ILC2 circuit
title Regulation of the tuft cell-ILC2 circuit in intestinal mucosal immunity
title_full Regulation of the tuft cell-ILC2 circuit in intestinal mucosal immunity
title_fullStr Regulation of the tuft cell-ILC2 circuit in intestinal mucosal immunity
title_full_unstemmed Regulation of the tuft cell-ILC2 circuit in intestinal mucosal immunity
title_short Regulation of the tuft cell-ILC2 circuit in intestinal mucosal immunity
title_sort regulation of the tuft cell ilc2 circuit in intestinal mucosal immunity
topic tuft cells
mucosal immunity
intestinal homeostasis
inflammatory bowel disease
tuft cell-ILC2 circuit
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568062/full
work_keys_str_mv AT kaiyushang regulationofthetuftcellilc2circuitinintestinalmucosalimmunity
AT xinxinqi regulationofthetuftcellilc2circuitinintestinalmucosalimmunity
AT tingtingtian regulationofthetuftcellilc2circuitinintestinalmucosalimmunity
AT huidongshi regulationofthetuftcellilc2circuitinintestinalmucosalimmunity
AT yuejiezhu regulationofthetuftcellilc2circuitinintestinalmucosalimmunity
AT fengbozhang regulationofthetuftcellilc2circuitinintestinalmucosalimmunity