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A TLR9 agonist promotes IL-22-dependent pancreatic islet allograft survival in type 1 diabetic mice.


ABSTRACT: Pancreatic islet transplantation is a promising potential cure for type 1 diabetes (T1D). Islet allografts can survive long term in the liver parenchyma. Here we show that liver NK1.1+ cells induce allograft tolerance in a T1D mouse model. The tolerogenic effects of NK1.1+ cells are mediated through IL-22 production, which enhances allograft survival and increases insulin secretion. Increased expression of NKG2A by liver NK1.1+ cells in islet allograft-transplanted mice is involved in the production of IL-22 and in the reduced inflammatory response to allografts. Vaccination of T1D mice with a CpG oligonucleotide TLR9 agonist (ODN 1585) enhances expansion of IL-22-producing CD3-NK1.1+ cells in the liver and prolongs allograft survival. Our study identifies a role for liver NK1.1+ cells, IL-22 and CpG oligonucleotides in the induction of tolerance to islet allografts in the liver parenchyma.

SUBMITTER: Tripathi D 

PROVIDER: S-EPMC5171644 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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A TLR9 agonist promotes IL-22-dependent pancreatic islet allograft survival in type 1 diabetic mice.

Tripathi Deepak D   Venkatasubramanian Sambasivan S   Cheekatla Satyanarayana S SS   Paidipally Padmaja P   Welch Elwyn E   Tvinnereim Amy R AR   Vankayalapati Ramakrishna R  

Nature communications 20161216


Pancreatic islet transplantation is a promising potential cure for type 1 diabetes (T1D). Islet allografts can survive long term in the liver parenchyma. Here we show that liver NK1.1<sup>+</sup> cells induce allograft tolerance in a T1D mouse model. The tolerogenic effects of NK1.1<sup>+</sup> cells are mediated through IL-22 production, which enhances allograft survival and increases insulin secretion. Increased expression of NKG2A by liver NK1.1<sup>+</sup> cells in islet allograft-transplant  ...[more]

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