Weekly injection of IL-2 using an injectable hydrogel reduces autoimmune diabetes incidence in NOD mice

Nadine Nagy, Gernot Kaber, Michael J. Kratochvil, Hedwich F. Kuipers, Shannon M. Ruppert, Koshika Yadava, Jason Yang, Sarah C. Heilshorn, S. Alice Long, Alberto Pugliese, Paul L. Bollyky

Research output: Contribution to journalArticlepeer-review

Abstract

Aims/hypothesis: IL-2 injections are a promising therapy for autoimmune type 1 diabetes but the short half-life of this cytokine in vivo limits effective tissue exposure and necessitates frequent injections. Here we have investigated whether an injectable hydrogel could be used to promote prolonged IL-2 release in vivo. Methods: Capitalising on the IL-2-binding capabilities of heparin, an injectable hydrogel incorporating clinical-grade heparin, collagen and hyaluronan polymers was used to deliver IL-2. The IL-2-release kinetics and in vivo stability of this material were examined. The ability of soluble IL-2 vs hydrogel-mediated IL-2 injections to prevent autoimmune diabetes in the NOD mouse model of type 1 diabetes were compared. Results: We observed in vitro that the hydrogel released IL-2 over a 12-day time frame and that injected hydrogel likewise persisted 12 days in vivo. Notably, heparin binding potentiates the activity of IL-2 and enhances IL-2- and TGFβ-mediated expansion of forkhead box P3-positive regulatory T cells (FOXP3+ Tregs). Finally, weekly administration of IL-2-containing hydrogel partially prevented autoimmune diabetes while injections of soluble IL-2 did not. Conclusions/interpretation: Hydrogel delivery may reduce the number of injections required in IL-2 treatment protocols for autoimmune diabetes. [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)152-158
Number of pages7
JournalDiabetologia
Volume64
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • Autoimmune
  • Controlled release
  • Diabetes
  • Heparin
  • Hyaluronan
  • Hydrogels
  • IL-2
  • Treg

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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