التفاصيل البيبلوغرافية
| العنوان: |
Islet-Derived eATP Fuels Autoreactive CD8+ T Cells and Facilitates the Onset of Type 1 Diabetes. |
| المؤلفون: |
Tezza, Sara, Vergani, Andrea, Bassi, Roberto, Dellepiane, Sergio, Nasr, Moufida Ben, D'Addio, Francesca, Usuelli, Vera, Fiorina, Paolo, Pezzolesi, Marcus G., Wasserfall, Clive H., Atkinson, Mark A., F'chtbauer, Ernst-Martin, Folli, Franco, Dhe-Paganon, Sirano, Ben Nasr, Moufida, Pezzolesi, Marcus Guy, Maestroni, Anna, Zuccotti, Gian Vincenzo, Füchtbauer, Ernst-Martin, Falzoni, Simonetta |
| المصدر: |
Diabetes; Oct2018, Vol. 67 Issue 10, p2038-2053, 16p |
| مصطلحات موضوعية: |
ADENOSINE triphosphate receptors, CD8 antigen, T cells, TYPE 1 diabetes, AUTOIMMUNE disease treatment, INFLAMMATION treatment, THERAPEUTICS |
| مستخلص: |
Extracellular ATP (eATP) activates T cells by engaging the P2X7R receptor. We identified two loss-of-function P2X7R mutations that are protective against type 1 diabetes (T1D) and thus hypothesized that eATP/P2X7R signaling may represent an early step in T1D onset. Specifically, we observed that in patients with newly diagnosed T1D, P2X7R is upregulated on CD8+ effector T cells in comparison with healthy control subjects. eATP is released at high levels by human/murine islets in vitro in high-glucose/inflammatory conditions, thus upregulating P2X7R on CD8+ T cells in vitro. P2X7R blockade with oxidized ATP reduces the CD8+ T cell-mediated autoimmune response in vitro and delays diabetes onset in NOD mice. Autoreactive CD8+ T-cell activation is highly dependent upon eATP/P2X7R-mediated priming, while a novel sP2X7R recombinant protein abrogates changes in metabolism and the autoimmune response associated with CD8+ T cells. eATP/P2X7R signaling facilitates the onset of autoimmune T1D by fueling autoreactive CD8+ cells and therefore represents a novel targeted therapeutic for the disorder. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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