ORIGINAL RESEARCH article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
This article is part of the Research TopicMechanisms and Novel Therapeutic Targets and Approaches for Mitochondrial Dysfunction in Neurological and Cardiovascular DiseasesView all 9 articles
Mitochondrial Transplantation Ameliorates Experimental Autoimmune Encephalomyelitis by Modulating the Th17/Treg Balance and Restoring Metabolic Homeostasis
Provisionally accepted
A Ram Lee1
Suh Won Yang1Seon-Yeong Lee1
Su Been Jeon1Hye yeon Kang1
JeongWon Choi1Jin Hyung Park1Ju Hyeon Park1Su Bin Son2
Yunju Jeong2Jung Hwan Lee1
Woojun Kim1*
Mi-La Cho1*- 1Catholic University of Korea, Seoul, Republic of Korea
- 2Kyung Hee University, Dongdaemun-gu, Republic of Korea
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Mitochondrial dysfunction has been increasingly implicated in the pathogenesis of multiple sclerosis (MS), contributing to oxidative stress, immune dysregulation, and neurodegeneration. Current therapies primarily target inflammation but do not adequately address mitochondrial impairment or progressive tissue damage. This study aimed to evaluate the therapeutic potential of mitochondrial transplantation in experimental autoimmune encephalomyelitis (EAE), a murine model of MS, by investigating its effects on immune modulation, mitochondrial function, and tissue integrity. EAE was induced in mice using myelin oligodendrocyte glycoprotein. Isolated mitochondria were administered intravenously, and clinical progression, spinal cord histology, immune cell populations, mitochondrial activity, fibrosis, and gut microbiota composition were assessed. Additionally, human peripheral blood mononuclear cells (PBMCs) from MS patients were co-cultured with mitochondria to examine ATP production, reactive oxygen species levels, and T cell differentiation. Mitochondrial transplantation significantly reduced EAE severity, spinal cord inflammation, demyelination, and fibrosis. Treated mice showed increased regulatory T (Treg) cells, reduced T helper 17 (Th17) cells, improved mitochondrial biogenesis, and decreased oxidative stress. Gut microbiome analysis revealed beneficial compositional changes. In human PBMCs, mitochondrial transfer enhanced ATP synthesis, suppressed mitochondrial ROS, and promoted Treg differentiation while inhibiting pro-inflammatory cytokines. Our findings suggest that mitochondrial transplantation restores mitochondrial function, rebalances immune responses, and mitigates neuroinflammation and fibrosis in EAE. This approach offers a novel therapeutic strategy for MS by addressing both metabolic and immunological drivers of disease progression.
Keywords: Experimental autoimmune encephalomyelitis (EAE), Mitochondria, Multiple Sclerosis, Spinal Cord, T cell
Received: 03 Sep 2025; Accepted: 04 Feb 2026.
Copyright: © 2026 Lee, Yang, Lee, Jeon, Kang, Choi, Park, Park, Son, Jeong, Lee, Kim and Cho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Woojun Kim
Mi-La Cho
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