Cutting edge: ST8Sia6-generated α-2,8-disialic acids mitigate hyperglycemia in multiple low-dose streptozotocin-induced diabetes

Paul J. Belmonte, Michael J. Shapiro, Matthew J. Rajcula, Shaylene A. McCue, Virginia Smith Shapiro

Research output: Contribution to journalArticlepeer-review

Abstract

The immune system contains a series of checks and balances that maintain tolerance and prevent autoimmunity. Sialic acid-binding Ig-type lectins (Siglecs) are cell surface receptors found on immune cells and inhibit inflammation by recruiting protein tyrosine phosphatases to ITIMs. Islet-resident macrophages express Siglec-E, and Siglec-E expression decreases on islet-resident macrophages as insulitis progresses in the NOD mouse. The sialyltransferase ST8Sia6 generates α-2,8-disialic acids that are ligands for Siglec-E in vivo. We hypothesized that engaging Siglec-E through ST8Sia6-generated ligands may inhibit the development of immune-mediated diabetes. Constitutive overexpression of ST8Sia6 in pancreatic β cells mitigated hyperglycemia in the multiple low-dose streptozotocin model of diabetes, demonstrating that engagement of this immune receptor facilitates tolerance in the setting of inflammation and autoimmune disease.

Original languageEnglish (US)
Pages (from-to)3071-3076
Number of pages6
JournalJournal of Immunology
Volume204
Issue number12
DOIs
StatePublished - Jun 15 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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