期刊
BIOMATERIALS
卷 72, 期 -, 页码 1-10出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.08.040
关键词
Autoimmunity; Immunoengineering; Immunomodulation; Nanoparticles; PRINT; PLGA; Phosphatidylserine; Tolerance; Transplantation
资金
- NC TRACS [100K1202]
- NIH [U19AI109784, 8-VP1-CA174425-04, T32-AI007273-25]
- UCRF UNC
- Cancer Research Institute
- National Defense Science and Engineering Graduate Fellowship
- PhRMA Foundation
- University Cancer Research Fund
- UNC Medical Scientists Training Program [NIGMS-2-T32-GM008719]
- [CA1068-A-10]
The possibility of engineering the immune system in a targeted fashion using biomaterials such as nanoparticles has made considerable headway in recent years. However, little is known as to how modulating the spatial presentation of a ligand augments downstream immune responses. In this report we show that geometric manipulation of phosphatidylserine (PS) through fabrication on rod-shaped PLGA nanoparticles robustly dampens inflammatory responses from innate immune cells while promoting T regulatory cell abundance by impeding effector T cell expansion. This response depends on the geometry of PS presentation as both PS liposomes and 1 micron cylindrical PS-PLGA particles are less potent signal inducers than 80 x 320 nm rod-shaped PS-PLGA particles for an equivalent dose of PS. We show that this immune tolerizing effect can be co-opted for therapeutic benefit in a mouse model of multiple sclerosis and an assay of organ rejection using a mixed lymphocyte reaction with primary human immune cells. These data provide evidence that geometric manipulation of a ligand via biomaterials may enable more efficient and tunable programming of cellular signaling networks for therapeutic benefit in a variety of disease states, including autoimmunity and organ rejection, and thus should be an active area of further research. (C) 2015 Published by Elsevier Ltd.
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