Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.628059
Keywords
autoimmunity; T cells; T regulatory cells; immune tolerance; systemic lupus erythematosus; graft-versus-host disease; nanoparticles; humanized mice
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Funding
- NIH [GM007205, HD097531, AI154935]
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This study introduces a method to produce acellular tolerogenic aAPCs using PLGA nanoparticles, which can induce human T cells to become functional Tregs and modulate systemic autoimmunity. It highlights the potential of using PLGA NPs as a targeted approach to repair IL-2 and/or TGF-beta defects in autoimmune diseases.
Artificial antigen-presenting cells (aAPCs) are synthetic versions of naturally occurring antigen-presenting cells (APCs) that, similar to natural APCs, promote efficient T effector cell responses in vitro. This report describes a method to produce acellular tolerogenic aAPCs made of biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and encapsulating IL-2 and TGF-beta for a paracrine release to T cells. We document that these aAPCs can induce both human CD4(+) and CD8(+) T cells to become FoxP3(+) T regulatory cells (Tregs). The aAPC NP-expanded human Tregs are functional in vitro and can modulate systemic autoimmunity in vivo in humanized NSG mice. These findings establish a proof-of-concept to use PLGA NPs as aAPCs for the induction of human Tregs in vitro and in vivo, highlighting the immunotherapeutic potential of this targeted approach to repair IL-2 and/or TGF-beta defects documented in certain autoimmune diseases such as systemic lupus erythematosus.
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