ArticleGastroenterology2020
Identification of a γc Receptor Antagonist That Prevents Reprogramming of Human Tissue-resident Cytotoxic T Cells by IL15 and IL21.
Article in Gastroenterology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 37 citations in OpenAlex.
- Beyond gluten-free diet: Novel therapeutic frontiers in celiac disease armamentarium.World journal of gastrointestinal pharmacology and therapeutics · 2026Review
- From gluten to therapeutics: molecular mechanisms of celiac disease and emerging alternatives to the gluten-free diet.Frontiers in pharmacology · 2026Review
- Article
- New Insights on Genes, Gluten, and Immunopathogenesis of Celiac Disease.Gastroenterology · 2024Review
- Article
- Role of age in dynamics of autoantibodies in pediatric Celiac disease.Italian journal of pediatrics · 2023Article
- Review
- In a large Juvenile Idiopathic Arthritis (JIA) cohort, concomitant celiac disease is associated with family history of autoimmunity and a more severe JIA course: a retrospective study.Pediatric rheumatology online journal · 2022Article
- Selective Targeting of IL-15Rα Is Sufficient to Reduce Inflammation.Frontiers in immunology · 2022Article
- IL-15Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- IL-15 and PIM kinases direct the metabolic programming of intestinal intraepithelial lymphocytes.Nature communications · 2021Article
- Potential impact of celiac disease genetic risk factors on T cell receptor signaling in gluten-specific CD4+ T cells.Scientific reports · 2021Article
- Current and emerging therapies for coeliac disease.Nature reviews. Gastroenterology & hepatology · 2021Review
- Tissue alarmins and adaptive cytokine induce dynamic and distinct transcriptional responses in tissue-resident intraepithelial cytotoxic T lymphocytes.Journal of autoimmunity · 2020Article
- Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsGamma chain (γc) cytokines (interleukin [IL]2, IL4, IL7, IL9, IL15, and IL21) signal via a common γc receptor. IL2 regulates the immune response, whereas IL21 and IL15 contribute to development of autoimmune disorders, including celiac disease. We investigated whether BNZ-2, a peptide designed to inhibit IL15 and IL21, blocks these cytokines selectively and its effects on intraepithelial cytotoxic T cells.
methodsWe obtained duodenal biopsies from 9 patients with potential celiac disease (positive results from tests for anti-TG2 but no villous atrophy), 30 patients with untreated celiac disease (with villous atrophy), and 5 patients with treated celiac disease (on a gluten-free diet), as well as 43 individuals without celiac disease (controls). We stimulated primary intestinal intraepithelial CD8
resultsDuodenal tissues from patients with untreated celiac disease had increased levels of messenger RNAs encoding IL15 receptor subunit alpha (IL15RA) and IL21 compared with tissues from patients with potential celiac disease and controls. Activation of intraepithelial cytotoxic T cells with IL15 or IL21 induced separate signaling pathways; incubation of the cells with IL15 and IL21 cooperatively increased their transcriptional activity, proliferation, and cytolytic properties. BNZ-2 specifically inhibited the effects of IL15 and IL21, but not of other γc cytokines.
conclusionsWe found increased expression of IL15RA and IL21 in duodenal tissues from patients with untreated celiac disease compared with controls. IL15 and IL21 cooperatively activated intestinal intraepithelial cytotoxic T cells. In particular, they increased their transcriptional activity, proliferation, and cytolytic activity. The peptide BNZ-2 blocked these effects, but not those of other γc cytokines, including IL2. BNZ-2 might be used to prevent cytotoxic T-cell-mediated tissue damage in complex immune disorders exhibiting upregulation of IL15 and IL21.
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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.