ArticleCellular and molecular gastroenterology and hepatology2017
Interferon-Alpha Promotes Th1 Response and Epithelial Apoptosis via Inflammasome Activation in Human Intestinal Mucosa.
Article in Cellular and molecular gastroenterology and hepatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Targeting epithelial IFN-I signaling restores barrier integrity in anti-TNF refractory Crohn's disease.Journal of Crohn's & colitis · 2026Article
- Microbial 10-oxostearic acid protects mice against colitis via the nuclear receptor PPARα.Nature microbiology · 2026Article
- Type I interferon signaling promotes mucosal inflammation in murine models of colitis.bioRxiv : the preprint server for biology · 2026Article
- The Type I Interferon Axis in Systemic Autoimmune Diseases: From Molecular Pathways to Targeted Therapy.Biomolecules · 2025Review
- Article
- SLE serum induces altered goblet cell differentiation and leakiness in human intestinal organoids.EMBO molecular medicine · 2024Article
- Role of IFN-α in Rheumatoid Arthritis.Current rheumatology reports · 2024Review
- Cytokines and Regulating Epithelial Cell Division.Current drug targets · 2024Review
- Coexistence of apoptosis, pyroptosis, and necroptosis pathways in celiac disease.Clinical and experimental immunology · 2023Article
- Lacrimal Gland Epithelial Cells Shape Immune Responses through the Modulation of Inflammasomes and Lipid Metabolism.International journal of molecular sciences · 2023Article
- An essential role of adenosine deaminase acting on RNA 1 in coeliac disease mucosa.Frontiers in immunology · 2023Article
- Organoids as tools for fundamental discovery and translation-a Keystone Symposia report.Annals of the New York Academy of Sciences · 2022Article
- The Inflammasome NLR Family Pyrin Domain-Containing Protein 3 (NLRP3) as a Novel Therapeutic Target for Idiopathic Pulmonary Fibrosis.The American journal of pathology · 2022Review
- A genetic screen identifies a protective type III interferon response to Cryptosporidium that requires TLR3 dependent recognition.PLoS pathogens · 2022Article
- Star Polymers as Non-Viral Carriers for Apoptosis Induction.Biomolecules · 2022Article
- TNF-α synergises with IFN-γ to induce caspase-8-JAK1/2-STAT1-dependent death of intestinal epithelial cells.Cell death & disease · 2021Article
- Programmed Cell Death in the Small Intestine: Implications for the Pathogenesis of Celiac Disease.International journal of molecular sciences · 2021Review
- The Effects of Interferons on Allogeneic T Cell Response in GVHD: The Multifaced Biology and Epigenetic Regulations.Frontiers in immunology · 2021Review
- Advances in Disease Mechanisms and Translational Technologies: Clinicopathologic Significance of Inflammasome Activation in Autoimmune Diseases.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
- Interferon γ and α Have Differential Effects on SAMHD1, a Potent Antiviral Protein, in Feline Lymphocytes.Viruses · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGOUND &
aimsSeveral lines of investigation suggest that interferon (IFN) alpha can alter human intestinal mucosa homeostasis. These include the endogenous production of IFN alpha in celiac disease or inflammatory bowel diseases, as well as the occurrence of intestinal side effects of exogenous IFN alpha used as a therapeutic tool. Here, we present an ex vivo translational approach to investigate the effects of IFN alpha on the human normal intestinal mucosa, as well as its underlying mechanisms.
methodsHuman normal colonic mucosa explants were cultured in the presence or absence of IFN alpha 2a. Epithelial homeostasis was assessed using the immunohistochemical marker of apoptosis M30. The Wnt inhibitor Dickkopf-Homolog-1 (DKK1) was assayed in the supernatants by enzyme-linked immunosorbent assay. Activation of the inflammasome (caspase-1/interleukin [IL]18) and of a Th1 response was determined by in situ detection of active caspase-1, as well as by measurement of mature IL18 production and the prototype Th1 cytokine IFN gamma by enzyme-linked immunosorbent assay. In addition, mechanistic studies were performed using the specific caspase-1 inhibitor Tyr-Val-Ala-Asp(OMe)-fluoromethylketone (YVAD-FMK), IL18-binding protein, neutralizing anti-IFN gamma, and anti-DKK1 antibodies.
resultsIFN alpha 2a elicited a rapid (24 hours) disruption of surface and crypt colonic epithelial cells via apoptosis that was variable in intensity among the 20 individuals studied. This apoptotic effect was dependent on the initiation of an IFN gamma response elicited by resident T box expressed in T cells-positive lamina propria cells. Both apoptosis and Th1 response were subordinated to active caspase-1 and IL18 production. Finally, neutralization of IFN gamma-induced DKK1 partially protected against IFN alpha-induced epithelial apoptosis.
conclusionsBy using an ex vivo model, we show an interindividual heterogeneity of IFN alpha effects. We show that IFN alpha is able to disrupt both epithelial and immune homeostasis in the human intestine, by activation of an innate immunity platform, the inflammasome, which drives a Th1 response and leads to epithelial barrier disruption.
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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.