The receptor for advanced glycation endproducts (RAGE) modulates T cell signaling
| العنوان: | The receptor for advanced glycation endproducts (RAGE) modulates T cell signaling |
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| المؤلفون: | James C. Reed, William M. Philbrick, Kevan C. Herold, Gabriel Betancur, Maria Korah, Paula Preston-Hurlburt, Carrie L. Lucas |
| المصدر: | PLoS ONE PLoS ONE, Vol 15, Iss 9, p e0236921 (2020) |
| بيانات النشر: | Public Library of Science, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, CD4-Positive T-Lymphocytes, Glycation End Products, Advanced, Male, endocrine system diseases, Receptor for Advanced Glycation End Products, ERK signaling cascade, CD8-Positive T-Lymphocytes, Jurkat cells, Biochemistry, RAGE (receptor), White Blood Cells, Jurkat Cells, 0302 clinical medicine, Endocrinology, Medical Conditions, Cell Signaling, Animal Cells, Medicine and Health Sciences, Cytotoxic T cell, Child, Staining, Multidisciplinary, Chemistry, T Cells, ZAP70, Signaling cascades, Cell Staining, Small interfering RNA, Nucleic acids, medicine.anatomical_structure, cardiovascular system, Medicine, Female, Signal transduction, Cellular Types, Research Article, Signal Transduction, Adult, Cell signaling, Adolescent, Endocrine Disorders, Science, T cell, Immune Cells, Immunology, Cytotoxic T cells, Research and Analysis Methods, Transfection, 03 medical and health sciences, Young Adult, medicine, Genetics, Diabetes Mellitus, Humans, cardiovascular diseases, Non-coding RNA, Molecular Biology Techniques, Molecular Biology, Inflammation, Blood Cells, nutritional and metabolic diseases, Biology and Life Sciences, Cell Biology, Gene regulation, 030104 developmental biology, Diabetes Mellitus, Type 1, Specimen Preparation and Treatment, Metabolic Disorders, Cancer research, RNA, Gene expression, human activities, CD8, 030215 immunology |
| الوصف: | The receptor for advanced glycation endproducts (RAGE) is expressed in T cells after activation with antigen and is constitutively expressed in T cells from patients at-risk for and with type 1 diabetes mellitus (T1D). RAGE expression was associated with an activated T cell phenotype, leading us to examine whether RAGE is involved in T cell signaling. In primary CD4+ and CD8+ T cells from patients with T1D or healthy control subjects, RAGE- cells showed reduced phosphorylation of Erk. To study T cell receptor signaling in RAGE+ or-T cells, we compared signaling in RAGE+/+ Jurkat cells, Jurkat cells with RAGE eliminated by CRISPR/Cas9, or silenced with siRNA. In RAGE KO Jurkat cells, there was reduced phosphorylation of Zap70, Erk and MEK, but not Lck or CD3ξ. RAGE KO cells produced less IL-2 when activated with anti-CD3 +/- anti-CD28. Stimulation with PMA restored signaling and (with ionomycin) IL-2 production. Silencing RAGE with siRNA also decreased signaling. Our studies show that RAGE expression in human T cells is associated with an activated signaling cascade. These findings suggest a link between inflammatory products that are found in patients with diabetes, other autoimmune diseases, and inflammation that may enhance T cell reactivity. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1577b344dad8e8c8a4dd810bf63d920fTest http://europepmc.org/articles/PMC7521722Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1577b344dad8e8c8a4dd810bf63d920f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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