ArticleThe Journal of experimental medicine2022
Epithelial HNF4A shapes the intraepithelial lymphocyte compartment via direct regulation of immune signaling molecules.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Crosstalk between the microbiota and intestinal γδ T cell compartments in health and IBD.Gut microbes · 2026Review
- Temporal transcriptomic profiling identifies core regulators in cytokine-induced gut barrier disruption in differentiated Caco-2 cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Single-cell profiling reveals diverse γδ T cell subsets in ulcerative colitis.Science immunology · 2026Article
- Expression of immune-related genes and possible regulatory mechanisms in ulcerative colitis.Frontiers in molecular biosciences · 2026Article
- Sex-Specific Concordance of Striatal Transcriptional Signatures of Opioid Addiction in Human and Rodent Brains.Biological psychiatry global open science · 2025Article
- Dysregulation of γδ intraepithelial lymphocytes precedes Crohn's disease-like ileitis.Science immunology · 2025Article
- Deciphering the immunocellular regulatory network in inflammatory bowel disease: from susceptibility genes to cellular effectors and toward precision therapies.Frontiers in immunology · 2025Review
- Early subclinical stages of the inflammatory bowel diseases: insights from human and animal studies.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- Identification and validation of biomarkers related to centrosome replication in ulcerative colitis based on bulk transcriptome, single-cell RNA sequencing and experiments.Frontiers in immunology · 2025Article
- Bone Marrow-Derived ABCC6 Is an Essential Regulator of Ectopic Calcification In Pseudoxanthoma Elasticum.The Journal of investigative dermatology · 2024Article
- Epithelial regulation of microbiota-immune cell dynamics.Mucosal immunology · 2024Review
- HNF4A-Bridging the Gap Between Intestinal Metaplasia and Gastric Cancer.Evolutionary bioinformatics online · 2024Article
- Mitogen-Activated Protein Kinase and Exploratory Nuclear Receptor Crosstalk in Cancer Immunotherapy.International journal of molecular sciences · 2023Review
- Article
- β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer.Cancer immunology research · 2023Article
- Article
- Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.Frontiers in endocrinology · 2023Review
- CD90 is not constitutively expressed in functional innate lymphoid cells.Frontiers in immunology · 2023Article
- Gut microbiota-derived fatty acid and sterol metabolites: biotransformation and immunomodulatory functions.Gut microbesReview
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocyte nuclear factor 4 α (HNF4A) is a highly conserved nuclear receptor that has been associated with ulcerative colitis. In mice, HNF4A is indispensable for the maintenance of intestinal homeostasis, yet the underlying mechanisms are poorly characterized. Here, we demonstrate that the expression of HNF4A in intestinal epithelial cells (IECs) is required for the proper development and composition of the intraepithelial lymphocyte (IEL) compartment. HNF4A directly regulates expression of immune signaling molecules including butyrophilin-like (Btnl) 1, Btnl6, H2-T3, and Clec2e that control IEC-IEL crosstalk. HNF4A selectively enhances the expansion of natural IELs that are TCRγδ+ or TCRαβ+CD8αα+ to shape the composition of IEL compartment. In the small intestine, HNF4A cooperates with its paralog HNF4G, to drive expression of immune signaling molecules. Moreover, the HNF4A-BTNL regulatory axis is conserved in human IECs. Collectively, these findings underscore the importance of HNF4A as a conserved transcription factor controlling IEC-IEL crosstalk and suggest that HNF4A maintains intestinal homeostasis through regulation of the IEL compartment.
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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.