ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Tissue-derived hedgehog proteins modulate Th differentiation and disease.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
62 citing papers in PubMed, 88 citations in OpenAlex.
- Hedgehog blockade in steroid-refractory sclerotic chronic graft-versus-host disease.British journal of haematology · 2021Trial
- The FOXA transcription factors in allergic airway disease and asthma.Frontiers in allergy · 2026Review
- Noncanonical UPR factor CREB3L2 drives immune evasion of triple-negative breast cancer through Hedgehog pathway modulation in T cells.Science advances · 2025Article
- Multiple signaling pathways in the frontiers of lung cancer progression.Frontiers in immunology · 2025Review
- A multidimensional toolkit for elucidating temporal trajectories in cell development in vivo.Development (Cambridge, England) · 2024Article
- Pharmacologic Hedgehog inhibition modulates the cytokine profile of osteolytic breast cancer cells.Journal of bone oncology · 2024Article
- Lasting differential gene expression of circulating CD8 T cells in chronic HCV infection with cirrhosis identifies a role for Hedgehog signaling in cellular hyperfunction.Frontiers in immunology · 2024Article
- The impact of the Hedgehog signal pathway on the tumor immune microenvironment of gastric adenocarcinoma by integrated analysis of scRNA-seq and RNA-seq datasets.Functional & integrative genomics · 2023Article
- Hedgehog Signaling Regulates Treg to Th17 Conversion Through Metabolic Rewiring in Breast Cancer.Cancer immunology research · 2023Article
- Hedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells.Science signaling · 2023Article
- Emerging Roles of Hedgehog Signaling in Cancer Immunity.International journal of molecular sciences · 2023Review
- The emerging roles of Hedgehog signaling in tumor immune microenvironment.Frontiers in oncology · 2023Review
- Cell-autonomous Hedgehog signaling controls Th17 polarization and pathogenicity.Nature communications · 2022Article
- Review
- Epithelial barrier dysfunction in ocular allergy.Allergy · 2022Review
- Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis.International journal of molecular sciences · 2022Article
- Hedgehog/GLI signaling in hematopoietic development and acute myeloid leukemia-From bench to bedside.Frontiers in cell and developmental biology · 2022Review
- The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease.Frontiers in immunology · 2022Article
- Basal Cell Carcinoma and Hedgehog Pathway Inhibitors: Focus on Immune Response.Frontiers in medicine · 2022Review
- Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies of complex immune-mediated diseases have indicated that many genetic factors, each with individual low risk, contribute to overall disease. It is therefore timely and important to characterize how immune responses may be subtly modified by tissue context. In this article, we explore the role of tissue-derived molecules in influencing the function of T cells, which, owing to their migratory nature, come into contact with many different microenvironments through their lifespan. Hedgehog (Hh) proteins act as secreted morphogens, providing concentration-dependent positional and temporal cell-fate specification in solid tissues. Hh signaling is required for embryogenesis and is important in postnatal tissue renewal and in malignancy. However, the function of Hh in dynamic, fluid systems, such as in mammalian immunity, is largely unknown. In this article, we show that Hh-dependent transcription in T cells promoted Th2 transcriptional programs and differentiation, exacerbating allergic disease. Of interest, expression of Sonic Hh increased in lung epithelial cells following the induction of allergic disease, and lung T cells upregulated Hh target gene expression, indicating that T cells respond to locally secreted Hh ligands in vivo. We show that Il4, the key Th2 cytokine, is a novel transcriptional target of Hh signals in T cells, providing one mechanism for the role of Hh in Th differentiation. We propose that Hh, secreted from inflamed, remodeling, or malignant tissue, can modulate local T cell function. Our data present an unexpected and novel role for tissue-derived morphogens in the regulation of fluid immune responses, with implications for allergy and tumor responses, suggesting new uses for anti-Hh therapeutics.
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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.