Engineered immunological niche directs therapeutic development in models of progressive multiple sclerosis

• 成果类型: Article
• 署名作者: Rad, Laila M.; Hughes, Kevin R.; Wheeler, Sydney N.; Decker, Joseph T.; Orbach, Sophia M.; Galvan, Angelica; Thornhill, Jasmine; Griffin, Kate, V; Turkistani, Hamza; Urie, Russell R.; Irani, David N.; Shea, Lonnie D.; Morris, Aaron H.
• 署名单位: University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9236
• DOI: 10.1073/pnas.2409852122
• 发表日期: 2025-02-18
• 关键词: nanoparticle platform; chemokine expression; immune tolerance; t-cells; induction; biomaterial; pathogenesis; ocrelizumab; disability; antibodies

摘要

Primary progressive multiple sclerosis (MS) is a demyelinating autoimmune disease with only a single class of FDA- approved treatment, B cell depletion. Novel treatments could emerge from a deeper understanding of the interplay between multiple cell types within diseased tissue throughout progression. We initially describe an engineered biomaterial-based immunological niche (IN) as a surrogate for diseased tissue to investigate immune cell function and phenotype dynamics throughout a chronic progressive mouse model of MS. Using these niches, we identify an array of dysregulated CC chemokine signaling as potential targets. We then develop antigen- loaded nanoparticles that reduce CC chemokine signaling, while delivering antigen. These nanoparticles serve as an antigen- specific treat-ment, and a single injection reduces disease burden, even if administered after sympto-matic disease onset. This report demonstrates proof of principle of a biomaterial scaffold as a diseased tissue surrogate that can monitor immune function, identify potential drug targets, and guide the development of a therapeutic