ArticleGastroenterology2011
Gut-tropic T cells that express integrin α4β7 and CCR9 are required for induction of oral immune tolerance in mice.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
What it found
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Who cites it
105 citing papers in PubMed, 195 citations in OpenAlex.
- Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial.Clinical and experimental immunology · 2015Trial
- Epithelial NF-κB shapes protective Treg cell responses to restrain intestinal inflammation.Nature communications · 2026Article
- Intestinal Microfold Cells Play a Critical Role in the Uptake and Oral Tolerance Mediated by Lysophosphatidylserine-Containing Lipidic Nanoparticles.Nanomaterials (Basel, Switzerland) · 2026Article
- Intestinal tissue-resident memory T cells: Characteristics, spatial heterogeneity, age-related dynamics, and roles in disease regulation.Journal of advanced research · 2026Review
- The Heteromeric Dopamine Receptor D2:D3 Controls the Gut Recruitment and Suppressive Activity of Regulatory T-Cells.International journal of molecular sciences · 2025Article
- Article
- Transport functions of intestinal lymphatic vessels.Nature reviews. Gastroenterology & hepatology · 2025Review
- Allergen-Encapsulating Nanoparticles Reprogram Pathogenic Allergen-Specific Th2 Cells to Suppress Food Allergy.Advanced healthcare materials · 2025Article
- The renaissance of oral tolerance: merging tradition and new insights.Nature reviews. Immunology · 2025Review
- Liver-draining portal lymph node responds to enteric nematode infection by generating highly parasite-specific follicular T helper and B cell responses.Frontiers in immunology · 2025Article
- Chemokinergic and Dopaminergic Signalling Collaborates through the Heteromer Formed by CCR9 and Dopamine Receptor D5 Increasing the Migratory Speed of Effector CD4International journal of molecular sciences · 2024Article
- MALTectomy and psoriasis risk in women: A prospective study in the French E3N prospective cohort.PloS one · 2024Observational
- Mechanisms and functions of intestinal vascular specialization.The Journal of experimental medicine · 2024Review
- GPR43 stimulation on TCRαβJournal of neuroinflammation · 2023Article
- Transcriptomic and Metabolomic Changes Reveal the Immunomodulatory Function of Casein Phosphopeptide-Selenium Chelate in Beagle Dogs.Veterinary sciences · 2023Article
- Beyond FOXP3: a 20-year journey unravelling human regulatory T-cell heterogeneity.Frontiers in immunology · 2023Review
- The intestinal microenvironment shapes macrophage and dendritic cell identity and function.Immunology letters · 2023Review
- Emerging roles of a chemoattractant receptor GPR15 and ligands in pathophysiology.Frontiers in immunology · 2023Review
- Beyond allergic progression: From molecules to microbes as barrier modulators in the gut-lung axis functionality.Frontiers in allergy · 2023Review
- Chemokine receptor CCR9 suppresses the differentiation of CD4Mucosal immunology · 2022Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsInduction of oral immune tolerance (OT) blocks proinflammatory responses to orally administered antigens and might be used to treat autoimmune conditions. We investigated whether gut-tropic T cells that express the integrin α4β7 and the chemokine receptor CCR9 are required for OT.
methodsSkin delayed-type hypersensitivity and experimental autoimmune encephalomyelitis were used to monitor OT in mice. To assess the role of receptors that mediate localization of lymphocytes to the gut (gut-homing receptors) in induction of OT, we studied CCR9(-/-) and β7(-/-) mice and also blocked the α4β7 ligand MAdCAM-1 in wild-type mice. We used DEREG and Scurfy mice to assess the role of Foxp3(+) regulatory T cells (Treg) and IL-10(-/-) and IL-10Rβ(-/-) mice to examine the role of interleukin (IL)-10 in induction of OT.
resultsOT could not be induced in CCR9(-/-) or β7(-/-) mice, or when MAdCAM-1 was blocked in wild-type mice, indicating that gut-homing receptors are required for oral tolerization. Consistent with the role of all-trans retinoic acid in inducing gut-homing T cells, OT could not be induced in mice depleted of vitamin A. OT was rescued in CCR9(-/-) mice following adoptive transfer of wild-type T cells, but not CCR9(-/-) or β7(-/-) T cells. Gut-homing T cells are therefore necessary and sufficient to induce OT. Wild-type Treg and IL-10 were required to restore OT to CCR9(-/-) mice, indicating that homing and functional differentiation of IL-10-producing Treg in the gut is required for OT. Conversely, transfer of CCR9(-/-) or β7(-/-) T cells to wild-type mice partially inhibited OT.
conclusionsExpression of CCR9 and α4β7 on T cells and their subsequent localization to the gut is required for induction of OT in mice. Therapies designed to block gut-homing receptors might, under some conditions, interfere with normal tolerogenic mechanisms in the intestinal mucosa.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.