ArticleDigestive diseases and sciences2012
Paradoxically increased FOXP3+ T cells in IBD do not preferentially express the isoform of FOXP3 lacking exon 2.
Article in Digestive diseases and sciences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Current Perspectives on the Inflammatory Bowel Disease Pathogenesis of Microbiota and the Gut-Brain Axis, and Emerging Therapeutics.Biomedicines · 2026Review
- The immunobiology and therapeutic potential of regulatory T cells in autoimmune diseases and allergic diseases.Frontiers in immunology · 2025Review
- A splice of life: the discovery, function, and clinical implications of FOXP3 isoforms in autoimmune disease.International immunology · 2024Review
- Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.Nature communications · 2024Article
- Regulatory T cell homeostasis: Requisite signals and implications for clinical development of biologics.Clinical immunology (Orlando, Fla.) · 2023Review
- Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease.Frontiers in immunology · 2023Review
- The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis.Clinical & translational immunology · 2022Article
- Co-Expression of FOXP3FL and FOXP3Δ2 Isoforms Is Required for Optimal Treg-Like Cell Phenotypes and Suppressive Function.Frontiers in immunology · 2021Article
- HLA-Restriction of Human Treg Cells Is Not Required for Therapeutic Efficacy of Low-Dose IL-2 in Humanized Mice.Frontiers in immunology · 2021Article
- Impaired estrogen signaling underlies regulatory T cell loss-of-function in the chronically inflamed intestine.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- IPEX as a Consequence of Alternatively Spliced FOXP3.Frontiers in pediatrics · 2020Review
- Immunological mechanisms underpinning faecal microbiota transplantation for the treatment of inflammatory bowel disease.Clinical and experimental immunology · 2020Review
- The Effect of Butyrate-Supplemented Parenteral Nutrition on Intestinal Defence Mechanisms and the Parenteral Nutrition-Induced Shift in the Gut Microbiota in the Rat Model.BioMed research international · 2019Article
- Mucosal Immunity Related to FOXP3Journal of Korean medical science · 2018Article
- Regulatory T Cells and Profile of FOXP3 Isoforms Expression in Peripheral Blood of Patients with Myelodysplastic Syndromes.Advances in hematology · 2018Article
- Alternative Splicing of FOXP3-Virtue and Vice.Frontiers in immunology · 2018Review
- Article
- Crossover Subsets of CD4Digestive diseases and sciences · 2017Article
- CD4 T Cells in IBD: Crossing the Line?Digestive diseases and sciences · 2017Article
- An expanded population of pathogenic regulatory T cells in giant cell arteritis is abrogated by IL-6 blockade therapy.Annals of the rheumatic diseases · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundForkhead box P3 (FOXP3)+ regulatory T cells (Tregs) are critical for controlling inflammation in the gastrointestinal tract. There is a paradoxical increase of mucosal FOXP3+ T cells in patients with inflammatory bowel disease (IBD). These FOXP3+ cells were recently shown to include interleukin (IL)-17A-producing cells in Crohn's disease, resembling Th17 cells implicated in autoimmune diseases. FOXP3 inhibits IL-17A production, but a naturally occurring splice variant of FOXP3 lacking exon 2 (Δexon2) cannot.
aimsWe hypothesized that IBD patients preferentially express the Δexon2 variant of FOXP3 so the paradoxically increased mucosal Tregs in IBD could represent cells expressing only Δexon2.
methodsWe used antibodies and primers that can distinguish between the full-length and Δexon2 splice variant of FOXP3 to evaluate expression of these isoforms in human intestinal tissue by immunohistochemistry and quantitative polymerase chain reaction (PCR), respectively.
resultsNo difference in the expression pattern of Δexon2 relative to full-length FOXP3 was seen in ulcerative colitis or Crohn's disease versus non-IBD controls. By immunofluorescence microscopy and flow cytometry, we also did not find individual cells which expressed FOXP3 protein exclusively in the Δexon2 isoform in either IBD or control tissue. FOXP3+ mucosal CD4+ T cells from both IBD and control specimens were able to make IL-17A in vitro after phorbol myristate acetate (PMA) and ionomycin stimulation, but these cells did not preferentially express Δexon2.
conclusionsOur data do not support the hypothesis that selective expression of FOXP3 in the Δexon2 isoform accounts for the inability of copious FOXP3+ T cells to inhibit inflammation or IL-17 expression in IBD.
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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.