دورية أكاديمية
Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity
| العنوان: | Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity |
|---|---|
| المؤلفون: | Jenkins, Benjamin J, Blagih, Julianna, Ponce-Garcia, Fernando M, Canavan, Mary, Gudgeon, Nancy, Eastham, Simon, Hill, David, Hanlon, Megan M, Ma, Eric H, Bishop, Emma L, Rees, April, Cronin, James G, Jury, Elizabeth C, Dimeloe, Sarah K, Veale, Douglas J, Thornton, Catherine A, Vousden, Karen H, Finlay, David K, Fearon, Ursula, Jones, Gareth W, Sinclair, Linda V, Vincent, Emma E, Jones, Nicholas |
| المصدر: | Cell Metabolism (2023) (In press). |
| بيانات النشر: | Elsevier BV |
| سنة النشر: | 2023 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | CD4 T cell, T cell, autoimmunity, canagliflozin, gliflozins, human, immunometabolism |
| الوصف: | Augmented T cell function leading to host damage in autoimmunity is supported by metabolic dysregulation, making targeting immunometabolism an attractive therapeutic avenue. Canagliflozin, a type 2 diabetes drug, is a sodium glucose co-transporter 2 (SGLT2) inhibitor with known off-target effects on glutamate dehydrogenase and complex I. However, the effects of SGLT2 inhibitors on human T cell function have not been extensively explored. Here, we show that canagliflozin-treated T cells are compromised in their ability to activate, proliferate, and initiate effector functions. Canagliflozin inhibits T cell receptor signaling, impacting on ERK and mTORC1 activity, concomitantly associated with reduced c-Myc. Compromised c-Myc levels were encapsulated by a failure to engage translational machinery resulting in impaired metabolic protein and solute carrier production among others. Importantly, canagliflozin-treated T cells derived from patients with autoimmune disorders impaired their effector function. Taken together, our work highlights a potential therapeutic avenue for repurposing canagliflozin as an intervention for T cell-mediated autoimmunity. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10171393/1/1-s2.0-S155041312300178X-main.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10171393Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10171393/1/1-s2.0-S155041312300178X-main.pdfTest https://discovery.ucl.ac.uk/id/eprint/10171393Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.D5908BD1 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |