Journal article
Towards programming immune tolerance through geometric manipulation of phosphatidylserine
Biomaterials, Vol.72, pp.1-10
12/2015
DOI: 10.1016/j.biomaterials.2015.08.040
PMCID: PMC4852957
PMID: 26325217
Abstract
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 × 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.
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•Geometric manipulation of a cell surface ligand can be used to modulate signaling output.•Nanorod PS programs anti-inflammatory responses in dendritic cells and prevents effector T cell activation.•Nanorod PS prevents disease in a mouse model of multiple sclerosis.•Nanorod PS prevents alloactivation of human T cells.
Details
- Title: Subtitle
- Towards programming immune tolerance through geometric manipulation of phosphatidylserine
- Creators
- Reid A Roberts - University of North Carolina at Chapel HillTimothy K Eitas - University of North Carolina at Chapel HillJames D Byrne - University of North Carolina at Chapel HillBrandon M Johnson - University of North Carolina at Chapel HillPatrick J Short - University of North Carolina at Chapel HillKaren P McKinnon - University of North Carolina at Chapel HillShannon Reisdorf - University of North Carolina at Chapel HillJ.Christopher Luft - University of North Carolina at Chapel HillJoseph M DeSimone - University of North Carolina at Chapel HillJenny P Ting - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- Biomaterials, Vol.72, pp.1-10
- DOI
- 10.1016/j.biomaterials.2015.08.040
- PMID
- 26325217
- PMCID
- PMC4852957
- NLM abbreviation
- Biomaterials
- ISSN
- 0142-9612
- eISSN
- 1878-5905
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100000884, name: Cancer Research Institute; DOI: 10.13039/100006808, name: University of North Carolina, award: PCT/US2014/064312
- Language
- English
- Date published
- 12/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiation Oncology
- Record Identifier
- 9984274756102771
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