Immunological microenvironment and targeted therapeutics in multiple sclerosis: new insights in crosstalk between immune niches and CNS

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) that predominantly affects young adults. However, current disease-modifying therapies demonstrate limited efficacy in addressing progressive disease subtypes, underscoring the urgent need for novel therapeut...

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Main Authors: Xiaodi Sun, Feng Zhang, Luojinyun Wang, Gyeore Lee, Sibo Yang, Daqiang Zhou, Bohao Chang, Bo Hu, Yifan Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1604987/full
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author Xiaodi Sun
Feng Zhang
Luojinyun Wang
Gyeore Lee
Sibo Yang
Daqiang Zhou
Bohao Chang
Bo Hu
Yifan Zhou
author_facet Xiaodi Sun
Feng Zhang
Luojinyun Wang
Gyeore Lee
Sibo Yang
Daqiang Zhou
Bohao Chang
Bo Hu
Yifan Zhou
author_sort Xiaodi Sun
collection DOAJ
description Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) that predominantly affects young adults. However, current disease-modifying therapies demonstrate limited efficacy in addressing progressive disease subtypes, underscoring the urgent need for novel therapeutic strategies. Here, we systematically review the neuroimmune interactions underlying the pathogenesis of MS, with a focus on three key aspects: the immune niche, immune cell types, and cell-based therapies. We first discuss the evolution of brain-immune concepts, from early notions of immune privilege to modern understandings of brain-border immune niches (meninges, choroid plexus, and perivascular spaces). These compartments serve as critical interfaces where peripheral immune cells interact with CNS-resident immune cells. We then analyze the roles of specific immune cell subsets (e.g., T/B cells, myeloid cells and microglia) in disease progression, highlighting their functional heterogeneity across different MS subtypes. Furthermore, we highlight emerging MS immunotherapies-including chimeric antigen receptor (CAR) T regimens, mesenchymal stem cell interventions, microbiome modulation, and nanodelivery systems, which strategically target mechanistic nodes spanning neuroimmune niche regulation, inflammatory cascade blockade, and CNS neurorestorative capacities.
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issn 1664-3224
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publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-1e7de606825a4fb9bb294b77cac7955e2025-08-20T03:58:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16049871604987Immunological microenvironment and targeted therapeutics in multiple sclerosis: new insights in crosstalk between immune niches and CNSXiaodi SunFeng ZhangLuojinyun WangGyeore LeeSibo YangDaqiang ZhouBohao ChangBo HuYifan ZhouMultiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) that predominantly affects young adults. However, current disease-modifying therapies demonstrate limited efficacy in addressing progressive disease subtypes, underscoring the urgent need for novel therapeutic strategies. Here, we systematically review the neuroimmune interactions underlying the pathogenesis of MS, with a focus on three key aspects: the immune niche, immune cell types, and cell-based therapies. We first discuss the evolution of brain-immune concepts, from early notions of immune privilege to modern understandings of brain-border immune niches (meninges, choroid plexus, and perivascular spaces). These compartments serve as critical interfaces where peripheral immune cells interact with CNS-resident immune cells. We then analyze the roles of specific immune cell subsets (e.g., T/B cells, myeloid cells and microglia) in disease progression, highlighting their functional heterogeneity across different MS subtypes. Furthermore, we highlight emerging MS immunotherapies-including chimeric antigen receptor (CAR) T regimens, mesenchymal stem cell interventions, microbiome modulation, and nanodelivery systems, which strategically target mechanistic nodes spanning neuroimmune niche regulation, inflammatory cascade blockade, and CNS neurorestorative capacities.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1604987/fullmultiple sclerosisautoimmuneneuroimmunecerebral immune nichestargeted therapy
spellingShingle Xiaodi Sun
Feng Zhang
Luojinyun Wang
Gyeore Lee
Sibo Yang
Daqiang Zhou
Bohao Chang
Bo Hu
Yifan Zhou
Immunological microenvironment and targeted therapeutics in multiple sclerosis: new insights in crosstalk between immune niches and CNS
Frontiers in Immunology
multiple sclerosis
autoimmune
neuroimmune
cerebral immune niches
targeted therapy
title Immunological microenvironment and targeted therapeutics in multiple sclerosis: new insights in crosstalk between immune niches and CNS
title_full Immunological microenvironment and targeted therapeutics in multiple sclerosis: new insights in crosstalk between immune niches and CNS
title_fullStr Immunological microenvironment and targeted therapeutics in multiple sclerosis: new insights in crosstalk between immune niches and CNS
title_full_unstemmed Immunological microenvironment and targeted therapeutics in multiple sclerosis: new insights in crosstalk between immune niches and CNS
title_short Immunological microenvironment and targeted therapeutics in multiple sclerosis: new insights in crosstalk between immune niches and CNS
title_sort immunological microenvironment and targeted therapeutics in multiple sclerosis new insights in crosstalk between immune niches and cns
topic multiple sclerosis
autoimmune
neuroimmune
cerebral immune niches
targeted therapy
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1604987/full
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