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Tolerogenic nanoparticles suppress central nervous system inflammation.

Authors
  • Kenison, Jessica E1, 2
  • Jhaveri, Aditi3
  • Li, Zhaorong4
  • Khadse, Nikita3
  • Tjon, Emily4
  • Tezza, Sara3
  • Nowakowska, Dominika3
  • Plasencia, Agustin3
  • Stanton, Vincent P Jr3
  • Sherr, David H1, 2
  • Quintana, Francisco J5, 6
  • 1 Department of Pathology, Boston University School of Medicine, Boston, MA 02118.
  • 2 Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118.
  • 3 AnTolRx, Inc., Cambridge, MA 02139.
  • 4 Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard University Medical School, Boston, MA 02115.
  • 5 Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard University Medical School, Boston, MA 02115; [email protected]
  • 6 Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142.
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Dec 15, 2020
Volume
117
Issue
50
Pages
32017–32028
Identifiers
DOI: 10.1073/pnas.2016451117
PMID: 33239445
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Therapeutic approaches for the induction of immune tolerance remain an unmet clinical need for the treatment of autoimmune diseases, including multiple sclerosis (MS). Based on its role in the control of the immune response, the ligand-activated transcription factor aryl hydrocarbon receptor (AhR) is a candidate target for novel immunotherapies. Here, we report the development of AhR-activating nanoliposomes (NLPs) to induce antigen-specific tolerance. NLPs loaded with the AhR agonist ITE and a T cell epitope from myelin oligodendrocyte glycoprotein (MOG)35-55 induced tolerogenic dendritic cells and suppressed the development of experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS, in preventive and therapeutic setups. EAE suppression was associated with the expansion of MOG35-55-specific FoxP3+ regulatory T cells (Treg cells) and type 1 regulatory T cells (Tr1 cells), concomitant with a reduction in central nervous system-infiltrating effector T cells (Teff cells). Notably, NLPs induced bystander suppression in the EAE model established in C57BL/6 × SJL F1 mice. Moreover, NLPs ameliorated chronic progressive EAE in nonobese diabetic mice, a model which resembles some aspects of secondary progressive MS. In summary, these studies describe a platform for the therapeutic induction of antigen-specific tolerance in autoimmune diseases.

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