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

Author

Listed:
  • Deepak Tripathi

    (Center for Biomedical Research, University of Texas Health Science Center at Tyler)

  • Sambasivan Venkatasubramanian

    (Center for Biomedical Research, University of Texas Health Science Center at Tyler)

  • Satyanarayana S. Cheekatla

    (Center for Biomedical Research, University of Texas Health Science Center at Tyler)

  • Padmaja Paidipally

    (Center for Biomedical Research, University of Texas Health Science Center at Tyler)

  • Elwyn Welch

    (Center for Biomedical Research, University of Texas Health Science Center at Tyler)

  • Amy R. Tvinnereim

    (Center for Biomedical Research, University of Texas Health Science Center at Tyler)

  • Ramakrishna Vankayalapati

    (Center for Biomedical Research, University of Texas Health Science Center at Tyler)

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.

Suggested Citation

  • Deepak Tripathi & Sambasivan Venkatasubramanian & Satyanarayana S. Cheekatla & Padmaja Paidipally & Elwyn Welch & Amy R. Tvinnereim & Ramakrishna Vankayalapati, 2016. "A TLR9 agonist promotes IL-22-dependent pancreatic islet allograft survival in type 1 diabetic mice," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13896
    DOI: 10.1038/ncomms13896
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