mTOR Activation Underlies Enhanced B Cell Proliferation and Autoimmunity in PrkcdG510S/G510S Mice
| العنوان: | mTOR Activation Underlies Enhanced B Cell Proliferation and Autoimmunity in PrkcdG510S/G510S Mice |
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| المؤلفون: | Marion Moreews, Anne-Laure Mathieu, Kevin Pouxvielh, Quentin Reuschlé, Annabelle Drouillard, Pénélope Dessay, Marie Meignien, Jiang Zhang, Lucie Fallone, Noëmi Rousseaux, Michelle Ainouze, Amaury Rey, Ommar Omarjee, Elodie Decembre, Vanina Lenief, Sophia Djebali, Olivier Thaunat, Marlène Dreux, Laurent Genestier, Thierry Defrance, Pauline Soulas-Sprauel, Antoine Marçais, Thierry Walzer, Alexandre Belot |
| المصدر: | The Journal of Immunology. 210:1209-1221 |
| بيانات النشر: | The American Association of Immunologists, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | Autosomal recessive PRKCD deficiency has previously been associated with the development of systemic lupus erythematosus in human patients, but the mechanisms underlying autoimmunity remain poorly understood. We introduced the Prkcd G510S mutation that we previously associated to a Mendelian cause of systemic lupus erythematosus in the mouse genome, using CRISPR-Cas9 gene editing. PrkcdG510S/G510S mice recapitulated the human phenotype and had reduced lifespan. We demonstrate that this phenotype is linked to a B cell–autonomous role of Prkcd. A detailed analysis of B cell activation in PrkcdG510S/G510S mice shows an upregulation of the PI3K/mTOR pathway after the engagement of the BCR in these cells, leading to lymphoproliferation. Treatment of mice with rapamycin, an mTORC1 inhibitor, significantly improves autoimmune symptoms, demonstrating in vivo the deleterious effect of mTOR pathway activation in PrkcdG510S/G510S mice. Additional defects in PrkcdG510S/G510S mice include a decrease in peripheral mature NK cells that might contribute to the known susceptibility to viral infections of patients with PRKCD mutations. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::e28e4ca99c9a490fb4e6995e6866d49eTest https://doi.org/10.4049/jimmunol.2200818Test |
| رقم الانضمام: | edsair.doi...........e28e4ca99c9a490fb4e6995e6866d49e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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