Tolerance induction by PLGA-encapsulated human MOG in a B cell- and antibody-driven model of Experimental Autoimmune Encephalomyelitis 2864
Year: 2025
Type: article
Abstract: Description Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) is an autoimmune CNS disorder mediated by T cell and autoantibody responses targeting MOG, leading to paralysis and vision loss. Unlike the B cell-independent EAE model induced with mouse MOG35-55 peptide, human MOG (hMOG) protein requires B cells, better reflecting MOGAD’s immune mechanisms. We investigated PLGA nanoparticles encapsulating hMOG in a B cell- and autoantibody-dependent EAE model. C57BL/6 wild-type (WT), B cell-deficient (μMt), and secretory immunoglobulin-deficient (AID-/-μs-/-) mice were immunized with hMOG. WT mice developed chronic EAE, while μMt and AID-/-μs-/- mice remained asymptomatic, confirming disease reliance on B cells and antibodies. Prophylactic PLGA(hMOG) treatment (days -7 and 0) prevented disease, and therapeutic administration (days 13 and 15) reduced severity. Treated mice exhibited lower serum anti-hMOG IgG, reduced Th1/Th17 cytokines, and decreased IL-6 in splenic B cells. CNS analysis revealed fewer CD4+ T cells, proving the efficacy of PLGA(hMOG) in modulating both T and B cell responses. Finally, using Lysozyme-specific B cells, we observed that PLGA(Lysozyme) nanoparticles directly modulated B cell activation in vivo in a T cell-independent manner. Our findings show that PLGA(hMOG) nanoparticles prevent and treat disease in a B cell- and antibody-dependent model, inducing T and B cell tolerance. The use of hMOG highlights the approach’s potential for future MOGAD therapies. Funding Sources Supported by The MOG project Foundation Topic Categories Therapeutic Approaches to Autoimmunity (THER)
Source: The Journal of Immunology
Institution: Northwestern University
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416449245
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