ArticleThe Journal of clinical investigation2018
Interaction between smoking and ATG16L1T300A triggers Paneth cell defects in Crohn's disease.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Gene-Environment Interactions in Inflammatory Bowel Disease: A Systematic Review of Human Epidemiologic Studies.Journal of Crohn's & colitis · 2025Pooled it
- Reactive oxygen species stimulate Paneth cell plasticity and diminish antimicrobial function.The EMBO journal · 2026Article
- Review
- Cytokine networks in Paneth cell regulation.Mucosal immunology · 2026Review
- Paneth cells as orchestrators of epithelial barrier defense and emerging therapeutic targets in inflammatory bowel disease.Seminars in immunopathology · 2026Review
- VGLL4 modulates Paneth cells and sustains intestinal homeostasis.EMBO reports · 2026Article
- Towards IBD Prediction and Prevention: The Contribution of Genetics and Genomics.Inflammatory bowel diseases · 2025Review
- Gene-environment interactions shape the host-microbial interface in inflammatory bowel disease.Nature immunology · 2025Review
- Guts for Self-Eating: Role of Autophagy in Gastrointestinal Health and Disease.Gastro hep advances · 2025Review
- Macrophage LRRK2 hyperactivity impairs autophagy and induces Paneth cell dysfunction.Science immunology · 2024Article
- Western diet reduces small intestinal intraepithelial lymphocytes via FXR-Interferon pathway.Mucosal immunology · 2024Article
- Ileal Paneth Cell Phenotype is a Cellular Biomarker for Pouch Complications in Ulcerative Colitis.Journal of Crohn's & colitis · 2024Article
- Differential Impact of Smoking on Methylome and Transcriptome in Crohn's Disease and Ulcerative Colitis.Inflammatory bowel diseases · 2024Article
- NADScience translational medicine · 2024Article
- Infection and inflammation stimulate expansion of a CD74The EMBO journal · 2023Article
- Review
- Crohn's disease: Why the ileum?World journal of gastroenterology · 2023Review
- Rosiglitazone Does Not Affect the Risk of Inflammatory Bowel Disease: A Retrospective Cohort Study in Taiwanese Type 2 Diabetes Patients.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Paneth cells as the cornerstones of intestinal and organismal health: a primer.EMBO molecular medicine · 2023Review
- The Current State of Care for Black and Hispanic Inflammatory Bowel Disease Patients.Inflammatory bowel diseases · 2023Review
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Authors and funding
14 authors.
Funding
Abstract
It is suggested that subtyping of complex inflammatory diseases can be based on genetic susceptibility and relevant environmental exposure (G+E). We propose that using matched cellular phenotypes in human subjects and corresponding preclinical models with the same G+E combinations is useful to this end. As an example, defective Paneth cells can subtype Crohn's disease (CD) subjects; Paneth cell defects have been linked to multiple CD susceptibility genes and are associated with poor outcome. We hypothesized that CD susceptibility genes interact with cigarette smoking, a major CD environmental risk factor, to trigger Paneth cell defects. We found that both CD subjects and mice with ATG16L1T300A (T300A; a prevalent CD susceptibility allele) developed Paneth cell defects triggered by tobacco smoke. Transcriptional analysis of full-thickness ileum and Paneth cell-enriched crypt base cells showed the T300A-smoking combination altered distinct pathways, including proapoptosis, metabolic dysregulation, and selective downregulation of the PPARγ pathway. Pharmacologic intervention by either apoptosis inhibitor or PPARγ agonist rosiglitazone prevented smoking-induced crypt apoptosis and Paneth cell defects in T300A mice and mice with conditional Paneth cell-specific knockout of Atg16l1. This study demonstrates how explicit G+E can drive disease-relevant phenotype and provides rational strategies for identifying actionable targets.
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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.