SLAM receptors foster iNKT cell development by reducing TCR signal strength after positive selection
| Autor: | Thierry Mallevaey, Virginie Calderon, André Veillette, Mayra Cruz Tleugabulova, Ming-Chao Zhong, Yan Lu, Jin Qian |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell Survival Immunology Phosphatase Receptors Antigen T-Cell chemical and pharmacologic phenomena Biology Proto-Oncogene Proteins c-fyn Article 03 medical and health sciences Mice 0302 clinical medicine FYN Antigen Downregulation and upregulation Costimulatory and Inhibitory T-Cell Receptors Signaling Lymphocytic Activation Molecule Family Immunology and Allergy Animals Humans Signaling Lymphocytic Activation Molecule Associated Protein Receptor Cell Proliferation Mice Knockout Cell growth Protein Tyrosine Phosphatase Non-Receptor Type 6 T-cell receptor hemic and immune systems Cell biology 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 embryonic structures Natural Killer T-Cells CD8 030215 immunology Signal Transduction |
| Zdroj: | Nature immunology. 20(4) |
| ISSN: | 1529-2916 |
| Popis: | Invariant natural killer T cells (iNKT cells) develop through an incompletely understood process that requires positive selection by CD4+CD8+ double-positive thymocytes and SLAM family receptors (SFRs). Here we found that SFRs promoted the development of iNKT cells by reducing the strength of the T cell antigen receptor (TCR) signal after positive selection. This effect improved the survival of iNKT cells and their responses to antigen. Loss of SFRs upregulated the expression of inhibitory receptors, including PD-1, on iNKT cells to mitigate the deleterious effect of SFR deficiency. The role of SFRs could be mimicked by expression of SLAMF6 alone in SFR-deficient mice, and this involved the adaptor SAP–kinase Fyn complex and the phosphatase SHP-1. Thus, SFRs foster iNKT cell development by attenuating TCR signal strength after positive selection. Veillette and colleagues show that receptors of the SLAM family promote the development of iNKT cells by reducing the strength of the TCR signal after positive selection. |
| Databáze: | OpenAIRE |
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