The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling
Open accessAbstract
The small intestinal tuft cell-ILC2 circuit mediates epithelial responses to intestinal helminths and protists by tuft cell chemosensory-like sensing and IL-25-mediated activation of lamina propria ILC2s. Small intestine ILC2s constitutively express the IL-25 receptor, which is negatively regulated by A20 (Tnfaip3). A20 deficiency in ILC2s spontaneously triggers the circuit and, unexpectedly, promotes adaptive small-intestinal lengthening and remodeling. Circuit activation occurs upon weaning and is enabled by dietary polysaccharides that render mice permissive for Tritrichomonas colonization, resulting in luminal accumulation of acetate and succinate, metabolites of the protist hydrogenosome. Tuft cells express GPR91, the succinate receptor, and dietary succinate, but not acetate, activates ILC2s via a tuft-, TRPM5-, and IL-25-dependent pathway. Also induced by parasitic helminths, circuit activation and small intestinal remodeling impairs infestation by new helminths, consistent with the phenomenon of concomitant immunity. We describe a metabolic sensing circuit that may have evolved to facilitate mutualistic responses to luminal pathosymbionts.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Tissue and circulating succinate is also elevated in other chronic inflammatory settings such as models of diet-induced obesity8.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [8]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites
Koh, A., De Vadder, F., Kovatcheva-Datchary, P., & Bäckhed, F. (2016) · Cell · doi:10.1016/j.cell.2016.05.041 · Cited by 7,070
The gut microbiota--masters of host development and physiology
Sommer, F., & Bäckhed, F. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro2974 · Cited by 3,681
Innate lymphoid cells — a proposal for uniform nomenclature
Spits, H., Artis, D., Colonna, M., Diefenbach, A., Disanto, J. D., Eberl, G., Koyasu, S., Locksley, R., McKenzie, A., Mebius, R., et al. (2013) · Nature reviews. Immunology · doi:10.1038/nri3365 · Cited by 2,380
Self-citationMills, E. L., Kelly, B., Logan, A., Costa, A. S. H., Varma, M., Bryant, C. E., Tourlomousis, P., Däbritz, J. H. M., Gottlieb, E., Latorre, I., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.064 · Cited by 2,291
Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity
Neill, D. R., Wong, S. H., Bellosi, A., Flynn, R. J., Daly, M. G., Langford, T. K. A., Bucks, C. M., Kane, C. M., Fallon, P. G., Pannell, R., et al. (2010) · Nature · doi:10.1038/nature08900 · Cited by 2,079
Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells
Moro, K., Yamada, T., Tanabe, M., Takeuchi, T., Ikawa, T., Kawamoto, H., Furusawa, J.-I., Ohtani, M., Fujii, H., & Koyasu, S. (2009) · Nature · doi:10.1038/nature08636 · Cited by 1,994
Snippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.016 · Cited by 1,951
Microbiota-mediated colonization resistance against intestinal pathogens
Buffie, C. G., & Pamer, E. G. (2013) · Nature reviews. Immunology · doi:10.1038/nri3535 · Cited by 1,564
Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus
Monticelli, L. A., Sonnenberg, G. F., Abt, M. C., Alenghat, T., Ziegler, C. G. K., Doering, T. A., Angelosanto, J., Laidlaw, B. J., Yang, C. Y., Sathaliyawala, T., et al. (2011) · Nature Immunology · doi:10.1038/ni.2131 · Cited by 1,327
Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus
Monticelli (2011) · PubMed · doi:10.1031/ni.2131 · Cited by 1,286
Cited by
Sorted by citations
Kennedy, E. A., King, K. Y., & Baldridge, M. T. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01534 · Cited by 602
Regulation of immune responses by the airway epithelial cell landscape
Hewitt, R. J., & Lloyd, C. M. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-020-00477-9 · Cited by 627
Cytokine Regulation and Function in T Cells
Dong, C. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-061020-053702 · Cited by 625
Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit
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., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.06.016 · Cited by 556
Self-citationEpithelial cell–derived cytokines: more than just signaling the alarm
Roan, F., Obata‐Ninomiya, K., & Ziegler, S. F. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124606 · Cited by 494
Metadata
- Authors
- Schneider, C., O’Leary, C. E., von Moltke, J., Liang, H.-E., Ang, Q. Y., Turnbaugh, P. J., Radhakrishnan, S., Pellizzon, M., Ma, A., & Locksley, R. M.
- Affiliations
- University of California, San Francisco (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Locksley, Richard M.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 174
- Issue
- 2
- Pages
- 271-284.e14
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6046262
- OpenAlex
- W2807333794
- Cited by
- 478
- References
- 54
- Citations by year
- 2026: 56 · 2025: 69 · 2024: 60 · 2023: 57 · 2022: 58 · 2021: 60 · 2020: 47 · 2019: 49 · 2018: 20
- FWCI
- 18.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (AI26918, AI30663, HL128903, HL122593)
- Howard Hughes Medical Institute
- Sandler Asthma Basic Research Center at the UCSF
- Swiss National Science Foundation (P2EZP3_162266, P300PA_171591)
- Nadia’s Gift Foundation Innovator
- Damon Runyon Cancer Research Foundation (DRR-42-16)
- UCSF Program for Breakthrough Biomedical Research
- Sandler Foundation
- Searle Scholars Program (SSP-2016-1352)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- tuft cells, ILC2, IL-25, A20, succinic acid, acetate, GPR91, TRPM5, Tritrichomonas, intestinal helminths, concomitant immunity, dietary polysaccharides, weaning
- MeSH terms
- Tumor Necrosis Factor alpha-Induced Protein 3, Acetates, Animals, Dietary Fiber, Energy Metabolism, Epithelial Cells, Interleukins, Intestinal Mucosa, Intestine, Small, Mice, Inbred C57BL, Mice, Transgenic, Plasmids, Tritrichomonas, Receptors, Interleukin, Succinic Acid, Receptors, G-Protein-Coupled, TRPM Cation Channels, Mice, Receptors, Interleukin-17, Microbiota
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 ›
Are you an author, or do you see a problem with this page? Request a review
