Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine
Open accessAbstract
Significance: Tuft cells in the intestine are known to act as sentinels for infectious agents [e.g., helminths (worms) and bacterial microbiota] and express taste-signaling elements. In this work, the G protein-coupled receptor Sucnr1 was shown to be expressed specifically in tuft cells but not in other intestinal epithelial cells. Dietary succinate and perturbations in the microbiota activate tuft cells, and subsequently type 2 immunity, via tuft cell-expressed Sucnr1. Modulating this pathway using dietary succinate or specific Sucnr1 agonists may be a strategy for fighting bacterial and parasitic infections or other type 2 immune-related metabolic disorders such as obesity.
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Succinate is increased in synovial fluids from rheumatoid arthritis patients.
“This correlates with an observed increase in succinate in synovial fluids from rheumatoid arthritis (RA) patients suggesting that chronically elevated succinate is pathological in this setting6.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [6]
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“Succinate activates Sucnr1 at millimolar or submillimolar ranges (21), and the type 2 immune responses were strongly evident when 100 mM succinate was ingested but barely detectable when 10 or 1 mM succinate was ingested (SI Appendix, Fig.”
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Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit
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- Authors
- Lei, W., Ren, W., Ohmoto, M., Urban, J. F., Matsumoto, I., Margolskee, R. F., & Jiang, P.
- Affiliations
- Monell Chemical Senses Center (US)
- Agricultural Research Service (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2018-05-07
- Volume
- 115
- Issue
- 21
- Pages
- 5552-5557
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6003470
- OpenAlex
- W2802153632
- Cited by
- 279
- References
- 51
- Citations by year
- 2026: 25 · 2025: 29 · 2024: 35 · 2023: 40 · 2022: 40 · 2021: 43 · 2020: 35 · 2019: 23 · 2018: 9
- FWCI
- 11.82
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1g20od020296-01, 1s10od018125-01a1)
- National Institute on Deafness and Other Communication Disorders (P30DC011735, R01DC014105)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- SUCNR1, G protein-coupled receptors, succinic acid, Th2 immune response, gut microbiota, small intestine, parasitic infection, bacterial infection, obesity, taste signaling
- MeSH terms
- Animals, Cells, Cultured, Epithelial Cells, Female, Intestine, Small, Male, Mice, Inbred C57BL, Nippostrongylus, Strongylida Infections, Mice, Knockout, Immunity, Mucosal, Succinic Acid, Goblet Cells, Receptors, G-Protein-Coupled, Cell Proliferation, Mice, Microbiota
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