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- Local immunomodulation Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance.
Local immunomodulation Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance.
Citation | “Local Immunomodulation Fas Ligand-Engineered Biomaterials Achieves Allogeneic Islet Graft Acceptance.”. Nature Materials, pp. 732-739. . |
Center | University of Michigan |
Author | 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 |
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 CD4CD25FoxP3 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. |
Year of Publication |
2018
|
Journal |
Nature materials
|
Volume |
17
|
Issue |
8
|
Number of Pages |
732-739
|
Date Published |
12/2018
|
ISSN Number |
1476-1122
|
DOI |
10.1038/s41563-018-0099-0
|
Alternate Journal |
Nat Mater
|
PMID |
29867165
|
PMCID |
PMC6060019
|
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