ArticleThe Journal of clinical investigation2008
The transcription factor IFN regulatory factor-4 controls experimental colitis in mice via T cell-derived IL-6.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 129 citations in OpenAlex.
- Defective expression of SIRT1 contributes to sustain inflammatory pathways in the gut.Mucosal immunology · 2014Trial
- Immunomodulatory and anti-inflammatory potential of S-nitrosoglutathione (GSNO) in multiple sclerosis: a review of mechanisms and therapeutic perspectives.Frontiers in immunology · 2026Review
- Macrophage-derived VISTA engages with LRIG1 and hinders gut epithelial repair in colitis.Cellular & molecular immunology · 2025Article
- Multiomic Integration Reveals Taxonomic Shifts Correlate to Serum Cytokines in an Antibiotics Model of Gut Microbiome Disruption.Cellular and molecular bioengineering · 2025Article
- Essential role of interferon-regulatory factor 4 in regulating diabetogenic CD4+ T and innate immune cells in autoimmune diabetes in NOD mice.Clinical and experimental immunology · 2025Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- MAdCAM-1 co-stimulation combined with retinoic acid and TGF-β induces blood CD8Mucosal immunology · 2024Article
- Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice.Nature communications · 2024Article
- Linking Periodontitis with Inflammatory Bowel Disease through the Oral-Gut Axis: The Potential Role ofBiomedicines · 2024Review
- NOD2-mediated dual negative regulation of inflammatory responses triggered by TLRs in the gastrointestinal tract.Frontiers in immunology · 2024Review
- Interferon regulatory factor 4 plays a pivotal role in the development of aGVHD-associated colitis.Oncoimmunology · 2024Article
- IRF4 is required for migration of CD4Frontiers in immunology · 2023Article
- Regulator of G-protein signaling 1 critically supports CD8Frontiers in immunology · 2023Article
- Intestinal homeostasis in the gut-lung-kidney axis: a prospective therapeutic target in immune-related chronic kidney diseases.Frontiers in immunology · 2023Review
- Expression levels of cellular inhibitor of apoptosis proteins and colitogenic cytokines are inversely correlated with the activation of interferon regulatory factor 4.Clinical and experimental immunology · 2022Article
- MYC-mediated early glycolysis negatively regulates proinflammatory responses by controlling IRF4 in inflammatory macrophages.Cell reports · 2021Article
- STAT3 determines IL-4 signalling outcomes in naïve T cells.Scientific reports · 2021Article
- AphaMaxNutrients · 2020Article
- A Synchronous IRF4-Dependent Gene Regulatory Network in B and Helper T Cells Orchestrating the Antibody Response.Trends in immunology · 2020Review
- Interleukin-9 Inhibits Lung Metastasis of Melanoma through Stimulating Anti-Tumor M1 Macrophages.Molecules and cells · 2020Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proinflammatory cytokine IL-6 seems to have an important role in the intestinal inflammation that characterizes inflammatory bowel diseases (IBDs) such as Crohn disease and ulcerative colitis. However, little is known about the molecular mechanisms regulating IL-6 production in IBD. Here, we assessed the role of the transcriptional regulator IFN regulatory factor-4 (IRF4) in this process. Patients with either Crohn disease or ulcerative colitis exhibited increased IRF4 expression in lamina propria CD3+ T cells as compared with control patients. Consistent with IRF4 having a regulatory function in T cells, in a mouse model of IBD whereby colitis is induced in RAG-deficient mice by transplantation with CD4+CD45RB(hi) T cells, adoptive transfer of wild-type but not IRF4-deficient T cells resulted in severe colitis. Furthermore, IRF4-deficient mice were protected from T cell-dependent chronic intestinal inflammation in trinitrobenzene sulfonic acid- and oxazolone-induced colitis. In addition, IRF4-deficient mice with induced colitis had reduced mucosal IL-6 production, and IRF4 was required for IL-6 production by mucosal CD90+ T cells, which it protected from apoptosis. Finally, the protective effect of IRF4 deficiency could be abrogated by systemic administration of either recombinant IL-6 or a combination of soluble IL-6 receptor (sIL-6R) plus IL-6 (hyper-IL-6). Taken together, our data identify IRF4 as a key regulator of mucosal IL-6 production in T cell-dependent experimental colitis and suggest that IRF4 might provide a therapeutic target for IBDs.
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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.