Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation
| Autor: | Ekati Drakopoulou, Divya K. Shah, Julian Dyson, Susan V. Outram, Marek Cebecauer, Ariadne L. Hager-Theodorides, Tessa Crompton, Nicola J. Rowbotham |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
CD4-Positive T-Lymphocytes
MAP Kinase Signaling System CD3 T cell Immunology Kruppel-Like Transcription Factors Receptors Antigen T-Cell Mice Transgenic Thymus Gland CD8-Positive T-Lymphocytes Zinc Finger Protein Gli2 CD5 Antigens Lymphocyte Activation Biochemistry Clonal deletion 03 medical and health sciences Mice 0302 clinical medicine Organ Culture Techniques medicine Animals Hedgehog Proteins Extracellular Signal-Regulated MAP Kinases 030304 developmental biology Immunobiology Cell Proliferation 0303 health sciences biology T-cell receptor Cell Biology Hematology Hedgehog signaling pathway Cell biology Thymocyte medicine.anatomical_structure biology.protein Signal transduction CD8 030215 immunology |
| Zdroj: | Blood |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | TCR signal strength is involved in many cell fate decisions in the T-cell lineage. Here, we show that transcriptional events induced by Hedgehog (Hh) signaling reduced TCR signal strength in mice. Activation of Hh signaling in thymocytes in vivo by expression of a transgenic transcriptional-activator form of Gli2 (Gli2\#916;N2) changed the outcome of TCR ligation at many stages of thymocyte development, allowing self-reactive cells to escape clonal deletion; reducing transgenic TCR-mediated positive selection; reducing the ratio of CD4/CD8 single-positive (SP) cells; and reducing cell surface CD5 expression. In contrast, in the Shh\#8722;/\#8722; thymus the ratio of CD4/CD8 cells and both positive and negative selection of a transgenic TCR were increased, demonstrating that Shh does indeed influence TCR repertoire selection and the transition from double-positive (DP) to SP cell in a physiological situation. In peripheral T cells, Gli2\#916;N2 expression attenuated T-cell activation and proliferation, by a mechanism upstream of ERK phosphorylation. |
| Databáze: | OpenAIRE |
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