MerTK is required for apoptotic cell–induced T cell tolerance
| العنوان: | MerTK is required for apoptotic cell–induced T cell tolerance |
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| المؤلفون: | H. Shelton Earp, Yaming Wang, Pradip Sen, Zuoan Yi, Clayton E. Mathews, Roland Tisch, Yingsu Huang, Mark A. Wallet, Bo Wang, Glenn K. Matsushima, Rafael Flores |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | CD8 Antigens, T-Lymphocytes, T cell, Immunology, Apoptosis, Mice, Transgenic, Cell Separation, Biology, C-Mer Tyrosine Kinase, Models, Biological, Article, Diabetes Mellitus, Experimental, Immune tolerance, Mice, 03 medical and health sciences, 0302 clinical medicine, Mice, Inbred NOD, Proto-Oncogene Proteins, Immune Tolerance, medicine, Animals, Immunology and Allergy, Transgenes, 030304 developmental biology, NOD mice, Wound Healing, 0303 health sciences, c-Mer Tyrosine Kinase, GAS6, Receptor Protein-Tyrosine Kinases, Articles, Dendritic Cells, MERTK, Flow Cytometry, Interleukin-12, CD11c Antigen, MERTK Gene, medicine.anatomical_structure, Interleukin 12, Cancer research, 030215 immunology |
| الوصف: | Self-antigens expressed by apoptotic cells (ACs) may become targets for autoimmunity. Tolerance to these antigens is partly established by an ill-defined capacity of ACs to inhibit antigen-presenting cells such as dendritic cells (DCs). We present evidence that the receptor tyrosine kinase Mer (MerTK) has a key role in mediating AC-induced inhibition of DC activation/maturation. Pretreatment of DCs prepared from nonobese diabetic (NOD) mice with AC blocked secretion of proinflammatory cytokines, up-regulation of costimulatory molecule expression, and T cell activation. The effect of ACs on DCs was dependent on Gas6, which is a MerTK ligand. NOD DCs lacking MerTK expression (NOD.MerTK(KD/KD)) were resistant to AC-induced inhibition. Notably, autoimmune diabetes was exacerbated in NOD.MerTK(KD/KD) versus NOD mice expressing the transgenic BDC T cell receptor. In addition, beta cell-specific CD4(+) T cells adoptively transferred into NOD.MerTK(KD/KD) mice in which beta cell apoptosis was induced with streptozotocin exhibited increased expansion and differentiation into type 1 T cell effectors. In both models, the lack of MerTK expression was associated with an increased frequency of activated pancreatic CD11c(+)CD8alpha(+) DCs, which exhibited an enhanced T cell stimulatory capacity. These findings demonstrate that MerTK plays a critical role in regulating self-tolerance mediated between ACs, DCs, and T cells. |
| تدمد: | 1540-9538 0022-1007 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ad262b536f2199d58fee22c1f3ef5ebaTest https://doi.org/10.1084/jem.20062293Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ad262b536f2199d58fee22c1f3ef5eba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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