c-Jun N-terminal kinase 1 defective CD4+CD25+FoxP3+ cells prolong pancreatic allograft survival in type 1 diabetic mice
| Autor: | Deepak Tripathi, Satyanarayana S. Cheekatla, Sambasivan Venkatasubramanian, Padmaja Paidipally, Elwyn Welch, Amy R. Tvinnereim, Ramakrishna Vankayalapati |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 198:82.37-82.37 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.198.supp.82.37 |
| Popis: | CD4+CD25+FoxP3+ cells (Tregs) inhibit inflammatory immune responses to allografts. Here we found that co-transplantation of allogeneic pancreatic islets with Tregs that are defective in JNK1 signaling prolong the islet allograft survival in the liver parenchyma of the T1D mice. Deletion of the JNK1 in Tregs increased the expression of anti-apoptotic molecules Mcl-1, Bcl-Xl and anti-inflammatory cytokine IL-10 production. JNK1−/− Tregs persist for long period in the transplanted liver and prolong the islet allograft survival compared to WT Tregs. JNK1−/− Tregs demonstrated improved control of allo-inflammation compared to WT Tregs in the T1D liver upon co-transplantation. JNK1−/− Tregs specifically inhibit IL-17 and IL-21 medited alloimmune response. Inhibition of alloimmune response by JNK1−/− Tregs independently mediated through the LAG3 on its cell surface and the increased production of IL-10. Our study identifies a novel role of JNK1 signaling in the Tregs function and co-transplantation of JNK1 deficient Tregs enhances the islet allograft survival in the liver parenchyma of T1D mice. |
| Databáze: | OpenAIRE |
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