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Reversal of Sjögren’s-like syndrome in non-obese diabetic mice
  1. Simon D Tran (simon.tran{at}mcgill.ca)
  1. McGill University, Canada
    1. Shohta Kodama (skodama{at}bics.bwh.harvard.edu)
    1. Brigham and Women’s Hospital, United States
      1. Beatrijs M Lodde (blodde{at}nidcr.nih.gov)
      1. NIH, United States
        1. Ildiko Szalayova (szalayoi{at}ninds.nih.gov)
        1. NIH, United States
          1. Sharon Key (keys{at}nidcr.nih.gov)
          1. NIH, United States
            1. Saeed Khalili (khalili.saeed{at}gmail.com)
            1. McGill University, Canada
              1. Denise L Faustman (faustman{at}helix.mgh.harvard.edu)
              1. Harvard Medical School, United States
                1. Eva Mezey (mezeye{at}nidcr.nih.gov)
                1. NIH, United States

                  Abstract

                  Objective: Non-obese diabetic (NOD) mice exhibit autoimmune diabetes and Sjögren’s-like syndrome. We tested if a therapy that reverses end-stage diabetes in the NOD mouse would affect their Sjögren’s-like syndrome.

                  Methods: NOD mice have a proteasome defect. Improperly selected naïve T cells escape but can be killed by re-introducing MHC class I-self peptides on matched normal splenocytes. The proteasome defect also impairs NFkB, a transcription factor in pathogenic memory T cells, increasing their susceptibility to TNF induced apoptosis stimulated via complete Freund’s adjuvant (CFA). We studied the impact of this two-limb therapy (injections of matched normal splenocytes and CFA) on the autoimmune salivary gland disease of the NOD mice.

                  Results: All NOD mice receiving the above therapy had a complete recovery of salivary flow and were protected from diabetes. Restoration of salivary flow could be a result of a combination of rescue and regeneration of the gland, as confirmed with immunohistochemistry. All untreated NOD mice showed a continuous decline in salivary flow, followed by hyperglycemia and death.

                  Conclusion: This study establishes that a brief intervention into NOD mice with Sjögren’s-like syndrome can reverse salivary gland dysfunction.

                  • MHC class I
                  • Sjögren’s syndrome
                  • proteasome
                  • regeneration
                  • salivary gland

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