Bioengineered particles expand myelin-specific regulatory T cells and reverse autoreactivity in a mouse model of multiple sclerosis-Reference-Cited by-同舟云学术

Bioengineered particles expand myelin-specific regulatory T cells and reverse autoreactivity in a mouse model of multiple sclerosis

Published:2023-06-02 Issue:22 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Rhodes Kelly R.¹²^ORCID,Tzeng Stephany Y.¹²^ORCID,Iglesias Marcos³^ORCID,Lee Dongwoo¹²,Storm Kaitlyn¹²^ORCID,Neshat Sarah Y.¹²^ORCID,VanDyke Derek²⁴^ORCID,Lowmaster Shirley M.¹²³,Spangler Jamie B.¹²⁴⁵⁶^ORCID,Raimondi Giorgio³^ORCID,Green Jordan J.¹²⁴⁵⁶^ORCID

Affiliation:

1. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

2. Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

3. Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

4. Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.

5. Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

6. Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by autoreactive immune cells damaging myelinated nerves, impairing brain function. Treatments aim for tolerance induction to reeducate the immune system to recognize myelin as “self” rather than “foreign.” As peripheral immune tolerance is primarily mediated by regulatory T cells (T regs ), we developed a therapy to support T reg expansion and activity in vivo. To target, engage, and activate myelin-specific T regs , we designed a biodegradable microparticle (MP) loaded with rapamycin and functionalized with a biased interleukin-2 (IL-2) fusion protein and a major histocompatibility complex (MHC) class II loaded with a myelin peptide. These tolerogenic MPs (Tol-MPs) were validated in vitro and then evaluated in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Tol-MPs promoted sustained disease reversal in 100% of mice and full recovery in 38% of mice with symptomatic EAE. Tol-MPs are a promising platform for treatment of autoimmune diseases.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.add8693

Reference54 articles.

1. Current landscape for T-cell targeting in autoimmunity and transplantation

2. Multiple sclerosis: Pathogenesis, symptoms, diagnoses and cell-based therapy;Ghasemi N.;Cell J,2017

3. Immunosuppressive treatments in multiple sclerosis

4. How regulatory T cells work

Cited by 15 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Multiple sclerosis treatments a review of current biomedical engineering approaches;Biomaterials;2025-02

2. Regulatory T Cells Nanoextinguisher to Manipulate Multiple Immune Evasion for Immunotherapy;ACS Nano;2024-08-22

3. A Literature Review and Meta-Analysis on the Potential Use of miR-150 as a Novel Biomarker in the Detection and Progression of Multiple Sclerosis;Journal of Personalized Medicine;2024-07-31

4. Intranasal Immunization of Pneumococcal pep27 Mutant Attenuates Allergic and Inflammatory Diseases by Upregulating Skin and Mucosal Tregs;Vaccines;2024-07-03

5. Regulatory T cells as a possible new target in epilepsy?;Epilepsia;2024-06-18