| First Author | Tripathi D | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 3310 |
| PubMed ID | 29459675 | Mgi Jnum | J:262623 |
| Mgi Id | MGI:6163148 | Doi | 10.1038/s41598-018-21477-9 |
| Citation | Tripathi D, et al. (2018) c-Jun N-terminal kinase 1 defective CD4+CD25+FoxP3+ cells prolong islet allograft survival in diabetic mice. Sci Rep 8(1):3310 |
| abstractText | 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 c-Jun N-terminal kinase 1 (JNK1) signaling prolongs islet allograft survival in the liver parenchyma of chemically induced diabetic mice (CDM). Adoptively transferred JNK1(-/-) but not wild-type (WT) Tregs survive longer in the liver parenchyma of CDM. JNK1(-/-) Tregs are resistant to apoptosis and express anti-apoptotic molecules. JNK1(-/-) Tregs express higher levels of lymphocyte activation gene-3 molecule (LAG-3) on their surface and produce higher amounts of the anti-inflammatory cytokine interleukin (IL)-10 compared with WT Tregs. JNK1(-/-) Tregs inhibit liver alloimmune responses more efficiently than WT Tregs. JNK1(-/-) but not WT Tregs are able to inhibit IL-17 and IL-21 production through enhanced LAG-3 expression and IL-10 production. Our study identifies a novel role of JNK1 signaling in Tregs that enhances islet allograft survival in the liver parenchyma of CDM. |
