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Adv. Sci., Feb 12 2025, | https://doi.org/10.1002/advs.202415265 Anti-Inflammatory Macrophage-Derived Exosomes Modified With Self-Antigen Peptides for Treatment of Experimental Autoimmune Encephalomyelitis

Qiaoyun Li ^{1 †}, Jinwon Park ^{1 †}, Jung Suk Kim ¹, Quoc-Viet Le ², Jaiwoo Lee ^{3 *}, Yu-Kyoung Oh ^{1 *}

¹College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
²Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, 700000, Vietnam.
³College of Pharmacy, Korea University, Sejong, 30019, Republic of Korea.

^†Q.L. and J.P. contributed equally to this work.
^*Corresponding authors: correspondence to Jaiwoo Lee or Yu-Kyoung Oh

Abstract

Current treatments for autoimmune diseases often involve broad-acting immunosuppressants, which carry risks such as infections and malignancies. This study investigates whether exosomes derived from anti-inflammatory macrophages (AE) and decorated with myelin oligodendrocyte glycoprotein (MOG) peptide (AE/M) can induce immune tolerance in autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis, serves as the autoimmune disease model. Exosomes derived from myoblasts or fibroblasts are also modified with MOG peptides for comparison. Unlike their myoblast or fibroblast counterparts, exosomes from anti-inflammatory macrophages demonstrate a targeted capacity toward antigen-presenting cells. Moreover, AE/M uniquely promotes the differentiation of dendritic cells (DC) into a tolerogenic phenotype. When splenocytes are treated with AE/M, an increased population of tolerogenic DC (tolDC) is observed, even under proinflammatory stimuli. Subcutaneous administration of AE/M in the EAE mouse model results in MOG peptide-specific immune tolerance and preserves motor coordination. In contrast to treatments with fibroblast- or myoblast-derived exosomes modified with MOG peptides, AE/M treatment provides complete protection from EAE in mice. These findings highlight the potential of self-antigen modified AE as a versatile and adaptable nanoplatform for the treatment of various autoimmune diseases.

논문정보

형식Research article
게재일2025년 02월 (BRIC 등록일 2025-02-13)
연구진국내(교신)+국외 연구진
분야 의약학 > 약학

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