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<p>Almost 1 million people in the United States suffer from multiple sclerosis&#xa0;(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 (MOG<sub>35-55</sub>) 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月23日

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  • Nicole Rose Lukesh,
  • Brian G. Barbery,
  • Kierstin A. Clark,
  • Luis Ontiveros-Padilla,
  • Stephen A. Ehrenzeller,
  • Ryan N. Woodring,
  • Sophie E. Mendell,
  • Denzel D. Middleton,
  • Md Jahirul Islam,
  • Erik S. Pena,
  • Dylan A. Hendy,
  • Sean R. Simpson,
  • Elizabeth G. Graham-Gurysh,
  • Alexandra M. Lopez,
  • Connor T. Murphy,
  • Grace L. Williamson,
  • Sophia A. Ly,
  • Kevin E. Shilling,
  • Elisa Landoni,
  • Rebeca T. Stiepel,
  • Delaney Sherwin,
  • Qi Ke,
  • Barbara Savoldo,
  • Gianpietro Dotti,
  • Yuliya Pylayeva-Gupta,
  • Roland M. Tisch,
  • Eric M. Bachelder,
  • Kristy M. Ainslie

摘要

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.