Themis controls thymocyte selection through regulation of T cell antigen receptor–mediated signaling
| Autor: | Guo Fu, Oreste Acuto, Jianfang Hu, Anil Munshi, Vasily Rybakin, Sébastien Vallée, Marielena V. McGuire, Claudia Brockmeyer, Mogjiborahman Salek, John A. H. Hoerter, Nicholas R. J. Gascoigne, Howard S Fox, Karsten Sauer, Yina H. Huang, Jeanette Ampudia, Paul R Fallen |
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| Rok vydání: | 2009 |
| Předmět: |
0303 health sciences
Cellular differentiation Immunology T-cell receptor FOXP3 hemic and immune systems chemical and pharmacologic phenomena Biology Article Cell biology 03 medical and health sciences Negative selection 0302 clinical medicine Antigen Immunology and Allergy IL-2 receptor Signal transduction Receptor 030304 developmental biology 030215 immunology |
| Zdroj: | Nature immunology |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | Themis (thymocyte-expressed molecule involved in selection), a member of a family of proteins with unknown functions, is highly conserved among vertebrates. Here we found that Themis had high expression in thymocytes between the pre-T cell antigen receptor (pre-TCR) and positive-selection checkpoints and low expression in mature T cells. Themis-deficient thymocytes showed defective positive selection, which resulted in fewer mature thymocytes. Negative selection was also impaired in Themis-deficient mice. A greater percentage of Themis-deficient T cells had CD4(+)CD25(+)Foxp3(+) regulatory and CD62L(lo)CD44(hi) memory phenotypes than did wild-type T cells. In support of the idea that Themis is involved in TCR signaling, this protein was phosphorylated quickly after TCR stimulation and was needed for optimal TCR-driven calcium mobilization and activation of the kinase Erk. |
| Databáze: | OpenAIRE |
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