Article Text

Download PDFPDF

1406 Acellular artificial antigen-presenting cells induce disease-protective immunoregulatory cells in lupus
  1. Antonio La Cava1 and
  2. David A Horwitz2
  1. 1University of California Los Angeles, Los Angeles, CA, USA
  2. 2General Nanotherapeutics, Santa Monica, CA, USA

Abstract

Background T regulatory cells (Tregs) provide beneficial effects in the suppression of autoimmune responses in systemic lupus erythematosus (SLE). We recently showed that poly(lactic-co-glycolic acid) PLGA nanoparticles (NPs) loaded with IL-2 and TGF-β could induce CD4+ and CD8+ Foxp3+ Tregs in vitro and in vivo, with resulting protective effects in mice that develop lupus-like disease following the transfer of donor T cells from DBA/2 mice into (C57BL/6 x DBA/2)F1 (BDF1) recipients.

Methods We produced NPs encapsulating IL-2 as acellular tolerogenic artificial antigen-presenting cell (aAPC)s for the induction of CD4+ and CD8+ Foxp3+ Tregs in vivo. aAPC NPs were also engineered to promote the tolerogenic activity of NK cells. Those acellular aAPCs were then tested for therapeutic efficacy in vivo in lupus-prone BDF1 mice.

Results The aAPC NPs induced CD4+ and CD8+ Tregs in vivo in BDF1 mice and protected the animals from lupus disease manifestations. At the NK cell level, protection from lupus-like disease could be ascribed to the production of TGF-β from the NP-induced NK cells. Finally, the use of aAPC NPs in humanized NSG mice expanded Tregs in numbers sufficient to protect mice from a rapidly evolving human anti-mouse graft-versus-host disease.

Conclusions These studies provide a proof-of-concept for the potential use of PLGA NPs as acellular aAPCs for the induction of therapeutically effective numbers of Tregs in conditions of pathologic deficit such as in SLE.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.