Towards programming immune tolerance through geometric manipulation of phosphatidylserine
| Autor: | Shannon Reisdorf, Joseph M. DeSimone, Reid A. Roberts, Patrick J. Short, Karen P. McKinnon, James D. Byrne, Timothy K. Eitas, Brandon M. Johnson, J. Christopher Luft, Jenny P.-Y. Ting |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cell signaling Materials science T cell Biophysics Down-Regulation Bioengineering Phosphatidylserines Lymphocyte Activation Article Immune tolerance Biomaterials Immune system Immune Tolerance medicine Animals Humans Myelin Sheath Inflammation Nanotubes Innate immune system Effector Dendritic Cells Mixed lymphocyte reaction Cell biology Mice Inbred C57BL Transplantation medicine.anatomical_structure Mechanics of Materials Immunology Ceramics and Composites Cytokines Particulate Matter |
| DOI: | 10.17615/1a9k-7q83 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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