ArticleCellular and molecular gastroenterology and hepatology2018
Indian Hedgehog Suppresses a Stromal Cell-Driven Intestinal Immune Response.
Article in Cellular and molecular gastroenterology and hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Intestinal epithelial cells in health and disease.Tissue barriers · 2026Review
- [Ecliptasaponin A ameliorates DSS-induced colitis in mice by suppressing M1 macrophage polarizationNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Stromal Cell Subsets Show Model-Dependent Changes in Experimental Colitis and Affect Epithelial Tissue Repair and Immune Cell Activation.Inflammatory bowel diseases · 2025Article
- Macrophage polarization in inflammatory bowel disease.Cell communication and signaling : CCS · 2023Review
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- The emerging roles of Hedgehog signaling in tumor immune microenvironment.Frontiers in oncology · 2023Review
- Region specificity of fibroblast-like cells in the mucosa of the rat large intestine.Cell and tissue research · 2022Article
- Tissue Niches Formed by Intestinal Mesenchymal Stromal Cells in Mucosal Homeostasis and Immunity.International journal of molecular sciences · 2022Review
- The Emerging Role of Hedgehog Signaling in Viral Infections.Frontiers in microbiology · 2022Review
- Emerging roles of the Hedgehog signalling pathway in inflammatory bowel disease.Cell death discovery · 2021Review
- The bright side of fibroblasts: molecular signature and regenerative cues in major organs.NPJ Regenerative medicine · 2021Review
- Epithelium-derived Indian Hedgehog restricts stromal expression of ErbB family members that drive colonic tumor cell proliferation.Oncogene · 2021Article
- Hedgehog Signaling in Intestinal Development and Homeostasis.Annual review of physiology · 2021Review
- Hedgehog Signaling in Colorectal Cancer: All in the Stroma?International journal of molecular sciences · 2021Review
- Stromal Cells in the Pathogenesis of Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2020Review
- Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid.The Journal of experimental medicine · 2020Article
- Hedgehog/GLI signaling in tumor immunity - new therapeutic opportunities and clinical implications.Cell communication and signaling : CCS · 2019Review
- Hedgehog Signaling Modulates Interleukin-33-Dependent Extrahepatic Bile Duct Cell Proliferation in Mice.Hepatology communications · 2019Article
- Features of a novel protein, rusticalin, from the ascidianMobile DNA · 2019Article
- Indian Hedgehog Suppresses Intestinal Inflammation.Cellular and molecular gastroenterology and hepatology · 2018Article
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsUpon intestinal epithelial damage a complex wound healing response is initiated to restore epithelial integrity and defend against pathogenic invasion. Epithelium-derived Indian Hedgehog (Ihh) functions as a critical sensor in this process. Signaling occurs in a paracrine manner because the receptor for Ihh is expressed only in the mesenchyme, but the exact Hedgehog target cell has remained elusive. The aim of this study was to elucidate further the nature of this target cell in the context of intestinal inflammation.
methodsHedgehog activity was modulated genetically in both cell type-specific and body-wide models and the resulting animals were analyzed for gene expression profiles and sensitivity for dextran sodium sulfate (DSS) colitis. To characterize the Hedgehog target cell,
resultsLoss of Indian Hedgehog from the intestinal epithelium resulted in a rapid increase in expression of inflammation-related genes, accompanied by increased influx of immune cells. Animals with epithelium-specific deletion of Ihh or lacking the Hedgehog receptor Smoothened from Hedgehog target cells were more sensitive to DSS colitis. In contrast, specific deletion of Smoothened in the myeloid compartment did not alter the response to DSS. This suggests that Hedgehog signaling does not repress intestinal immunity through an effect on myeloid cells. Indeed, we found that Hedgehog-responsive cells expressed gp38, smooth muscle actin, and desmin, indicating a fibroblastic nature. Ihh signaling inhibited expression of C-X-C motif chemokine ligand 12 (CXCL12) in fibroblasts in vitro and in vivo, thereby impairing the recruitment of immune cells.
conclusionsWe show that epithelium-derived Indian Hedgehog signals exclusively to fibroblasts in the intestine. Loss of Ihh leads to a rapid immune response with up-regulation of fibroblast-derived CXCL12, and migration of immune cells into the lamina propria.
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