ArticleProceedings of the National Academy of Sciences of the United States of America2015
Crohn's disease-derived monocytes fail to induce Paneth cell defensins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 65 citations in OpenAlex.
- A Novel Cationic Antimicrobial Peptide ScymidgutinProbiotics and antimicrobial proteins · 2026Article
- Tannic Acid and Ethacridine Lactate Attenuate Markers of Stress-Induced Intestinal Barrier Dysfunctions in Murine Small Intestinal Organoids.Biomolecules · 2025Article
- Antimicrobial overproduction sustains intestinal inflammation by inhibiting Enterococcus colonization.Cell host & microbe · 2023Article
- Human α-Defensin 5International journal of molecular sciences · 2023Article
- Mechanisms and regulation of defensins in host defense.Signal transduction and targeted therapy · 2023Review
- Ubiquitous Colonic Ileal Metaplasia Consistent with the Diagnosis of Crohn's Colitis among Indeterminate Colitis Cohorts.Medical research archives · 2023Article
- Myeloid vitamin D receptor regulates Paneth cells and microbial homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- Vitamin A- and D-Deficient Diets Disrupt Intestinal Antimicrobial Peptide Defense Involving Wnt and STAT5 Signaling Pathways in Mice.Nutrients · 2023Article
- Multifaceted involvements of Paneth cells in various diseases within intestine and systemically.Frontiers in immunology · 2023Review
- Food as Treatment of Inflammatory Bowel Diseases.Infection and immunity · 2022Review
- Palmitoylation in Crohn's disease: Current status and future directions.World journal of gastroenterology · 2021Review
- Exploring the Early Phase of Crohn's Disease.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2021Review
- Location is important: differentiation between ileal and colonic Crohn's disease.Nature reviews. Gastroenterology & hepatology · 2021Review
- Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn's Disease.Inflammatory bowel diseases · 2021Article
- Understanding the Molecular Drivers of Disease Heterogeneity in Crohn's Disease Using Multi-omic Data Integration and Network Analysis.Inflammatory bowel diseases · 2021Article
- The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier.Frontiers in nutrition · 2021Review
- Corrigendum: Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier.Frontiers in nutrition · 2021Article
- The roles and functions of Paneth cells in Crohn's disease: A critical review.Cell proliferation · 2021Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crohn's disease (CD) is associated with a multitude of genetic defects, many of which likely affect Paneth cell function. Paneth cells reside in the small intestine and produce antimicrobial peptides essential for the host barrier, principally human α-defensin 5 (HD5) and HD6. Patients with CD of the ileum are characterized by reduced constitutive expression of these peptides and, accordingly, compromised antimicrobial barrier function. Here, we present a previously unidentified regulatory mechanism of Paneth cell defensins. Using cultures of human ileal tissue, we showed that the secretome of peripheral blood mononuclear cells (PBMCs) from healthy controls restored the attenuated Paneth cell α-defensin expression characteristic of patients with ileal CD. Analysis of the Wnt pathway in both cultured biopsies and intestinal epithelial cells implicated Wnt ligands driving the PBMC effect, whereas various tested cytokines were ineffective. We further detected another defect in patients with ileal CD, because the PBMC secretomes derived from patients with CD were unable to restore the reduced HD5/HD6 expression. Accordingly, analysis of PBMC subtypes showed that monocytes of patients with CD express significantly lower levels of canonical Wnt ligands, including Wnt3, Wnt3a, Wnt1, and wntless Wnt ligand secretion mediator (Evi/Wls). These studies reveal an important cross-talk between bone marrow-derived cells and epithelial secretory Paneth cells. Defective Paneth cell-mediated innate immunity due to inadequate Wnt ligand stimulation by monocytes provides an additional mechanism in CD. Because defects of Paneth cell function stemming from various etiologies are overcome by Wnt ligands, this mechanism is a potential therapeutic target for this disease.
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