title: Genetic differentiation of poly I:C from B:9-23 peptide induced experimental autoimmune diabetes.
abstract: Type 1 diabetes is an immune-mediated disease, in which T cells of the adaptive immune system mediate beta cell destruction. Recently the innate immune system has been linked to etiopathogenesis of several autoimmune diseases including type 1 diabetes, as innate effector cells (e.g. dendritic cells, monocytes/macrophages and NK cells) can prime and promote or regulate (auto)immune responses. We have previously developed an experimental autoimmune diabetes (EAD) model with insulin peptide B:9-23 immunization in transgenic H-2(d)mice expressing the costimulatory molecule B7.1 in their islets (under the Rat Insulin Promotor, RIP). We compared the induction of diabetes with polyinosinic-polycytidylic acid (Poly I:C), a mimic of double stranded viral RNA versus insulin B:9-23 peptide in mice following backcrossing of the B7.1 transgene on to BALB/c mice from original B7.1 C57Bl/6 mice. We find that diabetes induction by Poly I:C is C57Bl/6 associated, whereas B:9-23 peptide induced diabetes and induction of insulin autoantibodies (IAA) are dependent on BALB/c genes. This B:9-23 peptide induced diabetes is consistent with MHC class II H-2(d)being necessary for the response to this peptide. Of note Poly I:C induction of diabetes was lost while B:9-23 induction was retained with backcrossing to BALB/c mice. Interaction of genes and environment (antigenic epitope and viral mimic) can be important in the pathogenesis of immune mediated diabetes and activation of the innate immune system (e.g. Poly I:C) may be one key determinant.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Box B140, Denver, CO 80262, USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Paronen
authors.forename: Edwin
authors.initials: E
authors.lastname: Liu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Devasenan
authors.initials: D
authors.lastname: Devendra
authors.forename: Akane
authors.initials: A
authors.lastname: Ide
authors.forename: Robert
authors.initials: R
authors.lastname: Taylor
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Dongmei
authors.initials: D
authors.lastname: Miao
authors.forename: Evie
authors.initials: E
authors.lastname: Melanitou
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage; D018122:B7-1 Antigen / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007113:Immunity, Innate; D007328:Insulin / Q000008:administration & dosage / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D011070:Poly I-C / Q000008:administration & dosage / Q000276:immunology*; D051381:Rats; D013045:Species Specificity
chemical_list: D001324:Autoantigens; D018122:B7-1 Antigen; D007328:Insulin; D010446:Peptide Fragments; C097877:insulin B (9-23); D011070:Poly I-C