Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit
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Abstract
In the small intestine, type 2 responses are regulated by a signaling circuit that involves tuft cells and group 2 innate lymphoid cells (ILC2s). Here, we identified the microbial metabolite succinate as an activating ligand for small intestinal (SI) tuft cells. Sequencing analyses of tuft cells isolated from the small intestine, gall bladder, colon, thymus, and trachea revealed that expression of tuft cell chemosensory receptors is tissue specific. SI tuft cells expressed the succinate receptor (SUCNR1), and providing succinate in drinking water was sufficient to induce a multifaceted type 2 immune response via the tuft-ILC2 circuit. The helminth Nippostrongylus brasiliensis and a tritrichomonad protist both secreted succinate as a metabolite. In vivo sensing of the tritrichomonad required SUCNR1, whereas N. brasiliensis was SUCNR1 independent. These findings define a paradigm wherein tuft cells monitor microbial metabolites to initiate type 2 immunity and suggest the existence of other sensing pathways triggering the response to helminths.
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HIF-1α expression is increased in synovial joints of rheumatoid arthritis patients.
“Intriguingly, HIF-1α expression is also increased in synovial joints of RA patients7 suggesting that succinate may act in two ways to increase inflammation in RA: via SUCNR1 and HIF-1α.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [7]
Inhibitors of α-KGDDs are often non-specific, hitting multiple isoforms or α-KGDD family members, such as DMOG acting on TETs but also PHDs.
“Inhibitors of α-KGDDs are often non-specific, either hitting multiple isoforms or a-KGDD family members, such as dimethyloxaloylglycine (DMOG) acting on TETs but also PHDs [7].”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [7]
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Coupling Krebs cycle metabolites to signalling in immunity and cancer
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- Authors
- Nadjsombati, M. S., McGinty, J. W., Lyons-Cohen, M. R., Jaffe, J. B., DiPeso, L., Schneider, C., Miller, C. N., Pollack, J. L., Nagana Gowda, G. A., Fontana, M. F., Erle, D. J., Anderson, M. S., Locksley, R. M., Raftery, D., & von Moltke, J.
- Affiliations
- University of Washington (US)
- Howard Hughes Medical Institute (US)
- University of California, San Francisco (US)
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 49
- Issue
- 1
- Pages
- 33-41.e7
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC6084797
- OpenAlex
- W2799094919
- Cited by
- 556
- References
- 71
- Citations by year
- 2026: 60 · 2025: 67 · 2024: 81 · 2023: 81 · 2022: 77 · 2021: 70 · 2020: 63 · 2019: 47 · 2018: 9
- FWCI
- 20.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- University of Washington (T32 AI106677)
- NIH (1DP2 OD024087, R01 AI26918)
- SABRE Center at the University of California, San Francisco
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- succinic acid, tuft cells, ILC2, Th2 immune response, SUCNR1, chemosensory receptors, microbial metabolites, small intestine, Nippostrongylus brasiliensis
- MeSH terms
- Animals, Cell Line, Female, Intestinal Mucosa, Intestine, Small, Male, Mice, Inbred C57BL, Nippostrongylus, Organ Specificity, Protozoan Infections, Species Specificity, Tritrichomonas, Signal Transduction, Strongylida Infections, Mice, Knockout, Th2 Cells, Immunity, Mucosal, Succinic Acid, Receptors, G-Protein-Coupled, TRPM Cation Channels
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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