ArticleJournal of autoimmunity2016
Sonic Hedgehog regulates thymic epithelial cell differentiation.
Article in Journal of autoimmunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Distinctive T-cell receptor repertoire in paediatric inflammatory multisystem syndrome temporally associated with coronavirus disease 2019/multisystem inflammatory syndrome in children patients: possible thymus involvement.Clinical and experimental immunology · 2025Article
- A multidimensional toolkit for elucidating temporal trajectories in cell development in vivo.Development (Cambridge, England) · 2024Article
- Cryopreservation of mouse thymus depletes thymocytes but supports immune reconstitution on transplantation.European journal of immunology · 2023Article
- The Hedgehog Pathway as a Therapeutic Target in Chronic Myeloid Leukemia.Pharmaceutics · 2023Review
- Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL).International journal of molecular sciences · 2023Review
- Human stem cell-derived thymic epithelial cells enhance human T-cell development in a xenogeneic thymus.The Journal of allergy and clinical immunology · 2022Article
- An essential function for autocrine hedgehog signaling in epithelial proliferation and differentiation in the trachea.Development (Cambridge, England) · 2022Article
- Thymus Functionality Needs More Than a Few TECs.Frontiers in immunology · 2022Review
- Differentiation of Pluripotent Stem Cells Into Thymic Epithelial Cells and Generation of Thymic Organoids: Applications for Therapeutic Strategies Against APECED.Frontiers in immunology · 2022Review
- Signaling Crosstalks Drive Generation and Regeneration of the Thymus.Frontiers in immunology · 2022Review
- A Spontaneous H2-Aa Point Mutation Impairs MHC II Synthesis and CD4Frontiers in immunology · 2022Article
- Review
- CXCL12-driven thymocyte migration is increased by thymic epithelial cells treated with prolactinJournal of biosciences · 2021Article
- Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation.The Journal of clinical investigation · 2019Article
- Thymic Epithelial Cells Contribute to Thymopoiesis and T Cell Development.Frontiers in immunology · 2019Review
- Sonic Hedgehog Is a Determinant of γδ T-Cell Differentiation in the Thymus.Frontiers in immunology · 2019Article
- Common Variable Immunodeficiency and Liver Involvement.Clinical reviews in allergy & immunology · 2018Review
- Foxa1 and Foxa2 in thymic epithelial cells (TEC) regulate medullary TEC and regulatory T-cell maturation.Journal of autoimmunity · 2018Article
- Gli3 in fetal thymic epithelial cells promotes thymocyte positive selection and differentiation by repression ofDevelopment (Cambridge, England) · 2018Article
- EphB receptors, mainly EphB3, contribute to the proper development of cortical thymic epithelial cells.Organogenesis · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Sonic Hedgehog (Shh) is expressed in the thymus, where it regulates T cell development. Here we investigated the influence of Shh on thymic epithelial cell (TEC) development. Components of the Hedgehog (Hh) signalling pathway were expressed by TEC, and use of a Gli Binding Site-green fluorescence protein (GFP) transgenic reporter mouse demonstrated active Hh-dependent transcription in TEC in the foetal and adult thymus. Analysis of Shh-deficient foetal thymus organ cultures (FTOC) showed that Shh is required for normal TEC differentiation. Shh-deficient foetal thymus contained fewer TEC than wild type (WT), the proportion of medullary TEC was reduced relative to cortical TEC, and cell surface expression of MHC Class II molecules was increased on both cortical and medullary TEC populations. In contrast, the Gli3-deficient thymus, which shows increased Hh-dependent transcription in thymic stroma, had increased numbers of TEC, but decreased cell surface expression of MHC Class II molecules on both cortical and medullary TEC. Neutralisation of endogenous Hh proteins in WT FTOC led to a reduction in TEC numbers, and in the proportion of mature Aire-expressing medullary TEC, but an increase in cell surface expression of MHC Class II molecules on medullary TEC. Likewise, conditional deletion of Shh from TEC in the adult thymus resulted in alterations in TEC differentiation and consequent changes in T cell development. TEC numbers, and the proportion of mature Aire-expressing medullary TEC were reduced, and cell surface expression of MHC Class II molecules on medullary TEC was increased. Differentiation of mature CD4 and CD8 single positive thymocytes was increased, demonstrating the regulatory role of Shh production by TEC on T cell development. Treatment of human thymus explants with recombinant Shh or neutralising anti-Shh antibody indicated that the Hedgehog pathway is also involved in regulation of differentiation from DP to mature SP T cells in the human thymus.
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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.