title: Localization of nucleic acid-sensing toll-like receptors in human and mouse pancreas.
abstract: Nucleic acid-sensing toll-like receptors (TLRs) (3, 7, 8, 9) have a role both in antiviral innate immunity and in autoimmune disorders. We assessed the expression of TLR3, 7, 8 and 9 in human and mouse pancreas focusing on the subpopulations of cells in the Langerhans islets. We studied eight human samples with normal pancreatic islets and two samples from patients with type 1 diabetes. Additionally, 10 CD-1 mouse pancreases were analysed. Immunohistochemical double-stainings for the TLRs and insulin, glucagon or somatostatin, respectively, were performed along with appropriate controls. In human pancreas, strong immunoreaction of TLR7 and TLR8 was observed in the insulin-positive beta cells, whereas glucagon- or somatostatin-expressing cells of the islets were weakly stained or negative. In type 1 diabetes, the expression in islets was weak or lost (TLR7: p = 0.014, TLR8: p = 0.053), correlating with loss of beta cells. TLR3 and 9 were expressed only weakly with no correlation with specific cell types. In mouse pancreas, only TLR9 was detected. Intra-pancreatic nerve ganglia strongly expressed TLR7. The strong expression of TLR7 and TLR8 in the beta cells of normal human islets could be an important piece in the puzzle of type 1 diabetes pathogenesis, and be linked with destruction of this particular subpopulation of the islet cells. In normal mice, only TLR9 can be constantly detected in the islets, highlighting differences between the species.
authors.affiliation: Department of Pathology, University of Oulu, Oulu, Finland.|Department of Surgery, University of Oulu, Oulu, Finland.|Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Helminen
authors.affiliation: Department of Pathology, University of Oulu, Oulu, Finland.|Department of Surgery, University of Oulu, Oulu, Finland.|Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Huhta
authors.affiliation: Department of Pathology, University of Oulu, Oulu, Finland.|Department of Surgery, University of Oulu, Oulu, Finland.|Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Joonas H
authors.initials: JH
authors.lastname: Kauppila
authors.affiliation: Department of Surgery, University of Oulu, Oulu, Finland.|Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Petri P
authors.initials: PP
authors.lastname: Lehenkari
authors.affiliation: Department of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Saarnio
authors.affiliation: Department of Pathology, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Karttunen
mesh_terms: D000818:Animals; D005260:Female; D005934:Glucagon / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000737:chemistry* / Q000276:immunology*; D008297:Male; D051379:Mice; D009696:Nucleic Acids / Q000378:metabolism*; D013004:Somatostatin / Q000032:analysis; D051193:Toll-Like Receptors / Q000032:analysis*
chemical_list: D007328:Insulin; D009696:Nucleic Acids; D051193:Toll-Like Receptors; D013004:Somatostatin; D005934:Glucagon
keywords: Toll-like receptor; autoimmunity; enterovirus; nucleic acid; type 1 diabetes