Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance

Devon M. Headen, Kyle B. Woodward, María M. Coronel, Pradeep Shrestha, Jessica D. Weaver, Hong Zhao, Min Tan, Michael D. Hunckler, William S. Bowen, Christopher T. Johnson, Lonnie Shea, Esma S. Yolcu, Andrés J. García, Haval Shirwan

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Islet transplantation is a promising therapy for type 1 diabetes. However, chronic immunosuppression to control rejection of allogeneic islets induces morbidities and impairs islet function. T effector cells are responsible for islet allograft rejection and express Fas death receptors following activation, becoming sensitive to Fas-mediated apoptosis. Here, we report that localized immunomodulation using microgels presenting an apoptotic form of the Fas ligand with streptavidin (SA-FasL) results in prolonged survival of allogeneic islet grafts in diabetic mice. A short course of rapamycin treatment boosted the immunomodulatory efficacy of SA-FasL microgels, resulting in acceptance and function of allografts over 200 days. Survivors generated normal systemic responses to donor antigens, implying immune privilege of the graft, and had increased CD4+CD25+FoxP3+ T regulatory cells in the graft and draining lymph nodes. Deletion of T regulatory cells resulted in acute rejection of established islet allografts. This localized immunomodulatory biomaterial-enabled approach may provide an alternative to chronic immunosuppression for clinical islet transplantation.

Original languageEnglish (US)
Pages (from-to)732-739
Number of pages8
JournalNature materials
Volume17
Issue number8
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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