Autoantigen-loaded Polymeric Microparticles associate with B cells and promote tolerogenic antigen presentation in a mouse model of experimental autoimmune encephalomyelitis

  • Nat Commun. 2026 Jun 23. doi: 10.1038/s41467-026-74641-5.
Nicole Rose Lukesh  1 ,  Brian G Barbery  1 ,  Kierstin A Clark  1 ,  Luis Ontiveros-Padilla  1 ,  Stephen A Ehrenzeller  1 ,  Ryan N Woodring  1 ,  Sophie E Mendell  1 ,  Denzel D Middleton  1 ,  Md Jahirul Islam  1 ,  Erik S Pena  2 ,  Dylan A Hendy  1 ,  Sean R Simpson  1 ,  Elizabeth G Graham-Gurysh  1 ,  Alexandra M Lopez  1 ,  Connor T Murphy  1 ,  Grace L Williamson  1 ,  Sophia A Ly  2 ,  Kevin E Shilling  1 ,  Elisa Landoni  3 ,  Rebeca T Stiepel  1 ,  Delaney Sherwin  3  4 ,  Qi Ke  5 ,  Barbara Savoldo  3  6 ,  Gianpietro Dotti  3  5 ,  Yuliya Pylayeva-Gupta  3  4 ,  Roland M Tisch  3  5 ,  Eric M Bachelder  1 ,  Kristy M Ainslie  7  8  9
Affiliations
  • 1. Division of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, UNC, Chapel Hill, NC, USA.
  • 2. Department of Biomedical Engineering, NC State/UNC, Chapel Hill, NC, USA.
  • 3. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
  • 4. Department of Genetics, School of Medicine, UNC, Chapel Hill, NC, USA.
  • 5. Department of Microbiology and Immunology, School of Medicine, UNC, Chapel Hill, NC, USA.
  • 6. Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA.
  • 7. Division of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, UNC, Chapel Hill, NC, USA. [email protected].
  • 8. Department of Biomedical Engineering, NC State/UNC, Chapel Hill, NC, USA. [email protected].
  • 9. Department of Microbiology and Immunology, School of Medicine, UNC, Chapel Hill, NC, USA. [email protected].
PMID: 42337240 DOI: 10.1038/s41467-026-74641-5
Abstract

Almost 1 million people in the United States suffer from Multiple Sclerosis (MS). Current therapies suppress protective immunity and are non-curative. Antigen-specific therapies can selectively suppress autoreactive cells, preserving protective immunity. B cell dysregulation, a major driver of MS, remains largely untargeted for antigen-specific tolerance. We hypothesize that targeting B cells with antigen-loaded microparticles will enhance therapeutic efficacy. Here, we demonstrate that antigen-loaded acetalated dextran microparticles (AMP) surface-associate with B cells and enhance IL-10 secretion and MHCII expression, promoting tolerogenic antigen presentation. Leveraging this property, we developed a therapy using myelin oligodendrocyte (MOG35-55) peptide-loaded AMPs associated with B cells (MOG-AMP-B). Administering MOG-AMP-Bs in a late therapeutic model of Multiple Sclerosis resulted in unprecedented recovery, reducing central nervous system (CNS) inflammation, downregulating activated dendritic cells and Macrophages, and increasing regulatory T- and B cells. MOG-AMP-Bs did not reduce the ability of Animals to respond to a Viral Infection, representing a highly effective antigen-specific therapy for restoring immune balance in autoimmunity.

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