Engineered immunological niches to monitor disease activity and treatment efficacy in relapsing multiple sclerosis

Aaron H. Morris, Kevin R. Hughes, Robert S. Oakes, Michelle M. Cai, Stephen D. Miller, David N. Irani, Lonnie D. Shea*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Relapses in multiple sclerosis can result in irreversible nervous system tissue injury. If these events could be detected early, targeted immunotherapy could potentially slow disease progression. We describe the use of engineered biomaterial-based immunological niches amenable to biopsy to provide insights into the phenotype of innate immune cells that control disease activity in a mouse model of multiple sclerosis. Differential gene expression in cells from these niches allow monitoring of disease dynamics and gauging the effectiveness of treatment. A proactive treatment regimen, given in response to signal within the niche but before symptoms appeared, substantially reduced disease. This technology offers a new approach to monitor organ-specific autoimmunity, and represents a platform to analyze immune dysfunction within otherwise inaccessible target tissues.

Original languageEnglish (US)
Article number3871
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

Funding

We would like to thank the UM Precision Health Scholars grant for funding this work. This work was supported in part by NIH grants R01AI148076, R01EB013198, R01DK121462, R21AI147677, and R01CA243916. A.H.M. is supported by a Michigan Life Science Fellows award and a NIH T32 grant DE007057-43 and would like to thank both of these funders for their support. We would like to thank Christopher Krebs, PhD and the University of Michigan DNA Sequencing Core for assistance in OpenArray processing and analysis. We would also like to thank the University of Michigan Flow Cytometry Core and In Vivo Animal Core for flow cytometry and histology resources, respectively. Thank you to Servier Medical Art for providing the cartoons of the mouse and syringe (modified and used in this paper) under a Creative Commons license: https://creativecommons.org/licenses/by/3.0/. Finally, we would like to thank Dr. Bethany Moore for helpful conversations and insights.

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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