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C-Jun N-terminal kinase 1 defective CD4+CD25+FoxP3+ cells prolong islet allograft survival in diabetic mice.


ABSTRACT: 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.

SUBMITTER: Tripathi D 

PROVIDER: S-EPMC5818514 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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c-Jun N-terminal kinase 1 defective CD4+CD25+FoxP3+ cells prolong islet allograft survival in diabetic mice.

Tripathi Deepak D   Cheekatla Satyanarayana S SS   Paidipally Padmaja P   Radhakrishnan Rajesh Kumar RK   Welch Elwyn E   Thandi Ramya Sivangala RS   Tvinnereim Amy R AR   Vankayalapati Ramakrishna R  

Scientific reports 20180219 1


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<sup>-/-</sup> but not wild-type (WT) Tregs survive longer in the liver parenchyma of CDM. JNK1<sup>-/-</sup> Tregs are resistant to apoptosis  ...[more]

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