Islet-specific expression of IL-10 promotes diabetes in nonobese diabetic mice independent of Fas, perforin, TNF receptor-1, and TNF receptor-2 molecules

B. Balasa, K. Van Gunst, N. Jung, D. Balakrishna, P. Santamaria, T. Hanafusa, N. Itoh, N. Sarvetnick

Research output: Contribution to journalArticle

40 Scopus citations


Several death-signaling or death-inducing molecules have been implicated in β cell destruction, including Fas, perforin, and TNFR-1. In this study, we examined the role of each death-signaling molecule in the IL-10-accelerated diabetes of nonobese diabetic (NOD) mice. Groups of IL-10-NOD mice, each deficient in either Fas, perforin, or TNFR-1 molecules, readily developed insulitis, and subsequently succumbed to diabetes with an accelerated kinetics and incidence similar to that observed in their wild-type or heterozygous IL-10-NOD littermates. Similarly, a TNFR-2 deficiency did not block accelerated diabetes in IL-10-NOD mice and spontaneous diabetes in NOD mice. These results demonstrate that pancreatic IL-10 promotes diabetes independent of Fas, perforin, TNFR-1, and TNFR-2 molecules. Subsequently, when cyclophosphamide, a diabetes-inducing agent, was injected into insulitis-free NOD.lpr/lpr mice, none of these mice developed insulitis or diabetes. Our data suggest that cyclophosphamide-but not IL-10-induced diabetes is Fas dependent. Overall, these findings provide evidence that pancreatic expression of IL-10 promotes diabetes independent of the major death pathways and provide impetus for identification of novel death pathways precipitating autoimmune destruction of insulin-producing β cells.

Original languageEnglish (US)
Pages (from-to)2841-2849
Number of pages9
JournalJournal of Immunology
Issue number5
Publication statusPublished - Sep 1 2000


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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