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Published on: April 6, 2015
Interleukin-18 Constrains the Intestinal Tuft Cell-Driven Responses During Helminth Infection
Mengyuan Dai1, Zhiqiang Yan1, Xinyu Lei1
1Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Interleukin-18 (IL-18) restrains type 2 immunity in the gut by inhibiting tuft cell responses. This finding reveals IL-18 as a crucial regulator for maintaining mucosal homeostasis during helminth infections.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Type 2 immunity at mucosal surfaces is vital for clearing helminths and maintaining tissue repair.
- Chemosensory tuft cells and group 2 innate lymphoid cells (ILC2s) form a key epithelial immune circuit.
- Regulatory mechanisms controlling this circuit's magnitude and duration are not fully understood.
Purpose of the Study:
- To identify regulatory mechanisms governing tuft cell-mediated type 2 immune responses at mucosal surfaces.
- To investigate the role of interleukin-18 (IL-18) in modulating type 2 immunity during helminth infection.
Main Methods:
- Utilized Interleukin-18-deficient (Il18-/-) and Interleukin-18 receptor-deficient (Il18r1-/-) mouse models.
- Employed Nippostrongylus brasiliensis infection model and small intestinal organoid cultures.
- Analyzed gene expression, cell lineage expansion, and signaling pathways (p38 MAPK).
Main Results:
- IL-18 deficiency led to increased tuft cell lineage expansion and enhanced type 2 immune responses during helminth infection.
- Tuft cells express IL-18 receptor alpha (IL-18Rα), indicating direct responsiveness to IL-18.
- IL-18 directly inhibited IL-13-induced tuft cell differentiation, proliferation, and gene expression via p38 MAPK signaling.
Conclusions:
- IL-18 acts as a negative feedback regulator, constraining tuft cell-mediated type 2 epithelial responses during helminth infection.
- This regulation by IL-18 is essential for balancing protective anti-helminth immunity with mucosal homeostasis.
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