Genetic differentiation of Poly I:C from B:9-23 peptide induced experimental autoimmune diabetes

Johanna Paronen 1, 2, 3 Edwin Liu 1 Hiroaki Moriyama 1 Devasenan Devendra 1 Akane Ide 1 Robert Taylor 1 Liping Yu 1 Dongmei Miao 1 Evie Melanitou 4, 1 George Eisenbarth 1, *
* Corresponding author
1 BDC - Barbara Davis Center for Childhood Diabetes
2 University of Helsinki [Helsinki]
3 THL - National Public Health Institute [Finland]
4 Institut Pasteur [Paris]
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.
Keywords : B:9-23 peptide Poly I:C Experimental autoimmune diabetes
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Johanna Paronen, Edwin Liu, Hiroaki Moriyama, Devasenan Devendra, Akane Ide, et al.. Genetic differentiation of Poly I:C from B:9-23 peptide induced experimental autoimmune diabetes. Journal of Autoimmunity, Elsevier, 2004, 22 (4), pp.307 - 313. ⟨10.1016/j.jaut.2004.01.006⟩. ⟨pasteur-01643774⟩

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