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Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression

  • Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)
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Abstract

Recent evidence has highlighted the role of the innate immune system in type 1 diabetes (T1D) pathogenesis. Specifically, aberrant activation of the interferon response prior to seroconversion of T1D-associated autoantibodies supports a role for the interferon response as a precipitating event toward activation of autoimmunity. Melanoma differentiation-associated protein 5 (MDA5), encoded by IFIH1, mediates the innate immune system’s interferon response to certain viral species that form double-stranded RNA (dsRNA), the MDA5 ligand, during their life cycle. Extensive research has associated single nucleotide polymorphisms (SNPs) within the coding region of IFIH1 with T1D. This review discusses the different risk and protective IFIH1 alleles in the context of recent structural and functional analysis that relate to MDA5 regulation of interferon responses. These studies have provided a functional hypothesis for IFIH1 T1D-associated SNPs’ effects on MDA5-mediated interferon responses as well as supporting the genome-wide association (GWA) studies that first associated IFIH1 with T1D.

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Acknowledgments

This work was supported by National Institutes of Health Grant PO1 A142288.

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Conflict of Interest

Benjamin M. Looney, Chang-Qing Xia, Patrick Concannon, David A. Ostrov, and Michael J. Clare-Salzler declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Pathology, Immunology and Laboratory Medicine, College of Medicine Interdisciplinary Program in Biomedical Sciences, University of Florida, 1600 SW Archer Rd., Gainesville, FL, 32610, USA

    Benjamin M. Looney

  2. Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, 1600 SW Archer Rd., Gainesville, FL, 32610, USA

    Chang-Qing Xia

  3. University of Florida Genetics Institute, 2033 Mowry Rd., P.O. Box 103610, Gainesville, FL, 32611, USA

    Patrick Concannon

  4. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, 2033 Mowry Rd., P.O. Box 103633, Gainesville, FL, 32611, USA

    David A. Ostrov & Michael J. Clare-Salzler

  5. Center for Immunology and Transplantation, University of Florida, 1600 SW Archer Rd., P.O. Box 100275, Gainesville, FL, 32610, USA

    Michael J. Clare-Salzler

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  1. Benjamin M. Looney
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Correspondence to Michael J. Clare-Salzler.

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This article is part of the Topical Collection on Pathogenesis of Type 1 Diabetes

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Looney, B.M., Xia, CQ., Concannon, P. et al. Effects of Type 1 Diabetes-Associated IFIH1 Polymorphisms on MDA5 Function and Expression. Curr Diab Rep 15, 96 (2015). https://doi.org/10.1007/s11892-015-0656-8

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