title: 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.
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas 75708, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Tripathi
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas 75708, USA.
authors.forename: Sambasivan
authors.initials: S
authors.lastname: Venkatasubramanian
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas 75708, USA.
authors.forename: Satyanarayana S
authors.initials: SS
authors.lastname: Cheekatla
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas 75708, USA.
authors.forename: Padmaja
authors.initials: P
authors.lastname: Paidipally
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas 75708, USA.
authors.forename: Elwyn
authors.initials: E
authors.lastname: Welch
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas 75708, USA.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Tvinnereim
authors.affiliation: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas 75708, USA.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Vankayalapati
mesh_terms: D000818:Animals; D018899:CpG Islands; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D006085:Graft Survival; D007378:Interleukins / Q000378:metabolism*; D007515:Islets of Langerhans / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000819:agonists*; D014611:Vaccination; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D000097043:Interleukin-22