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Astrocytic tight junctions control inflammatory CNS lesion pathogenesis
Open accessAbstract
Lesions and neurologic disability in inflammatory CNS diseases such as multiple sclerosis (MS) result from the translocation of leukocytes and humoral factors from the vasculature, first across the endothelial blood-brain barrier (BBB) and then across the astrocytic glia limitans (GL). Factors secreted by reactive astrocytes open the BBB by disrupting endothelial tight junctions (TJs), but the mechanisms that control access across the GL are unknown. Here, we report that in inflammatory lesions, a second barrier composed of reactive astrocyte TJs of claudin 1 (CLDN1), CLDN4, and junctional adhesion molecule A (JAM-A) subunits is induced at the GL. In a human coculture model, CLDN4-deficient astrocytes were unable to control lymphocyte segregation. In models of CNS inflammation and MS, mice with astrocyte-specific Cldn4 deletion displayed exacerbated leukocyte and humoral infiltration, neuropathology, motor disability, and mortality. These findings identify a second inducible barrier to CNS entry at the GL. This barrier may be therapeutically targetable in inflammatory CNS disease.
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“The glia limitans and basement membranes also create a barrier between circulating components of the immune system and the CNS parenchyma, a division that is integral to the neuroimmune axis (42).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [42]
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Coll, R. C., Robertson, A. A. B., Chae, J. J., Higgins, S. C., Muñoz-Planillo, R., Inserra, M. C., Vetter, I., Dungan, L. S., Monks, B. G., Stutz, A., et al. (2015) · Nature Medicine · doi:10.1038/nm.3806 · Cited by 2,849
Development, maintenance and disruption of the blood-brain barrier
Obermeier, B., Daneman, R., & Ransohoff, R. M. (2013) · Nature Medicine · doi:10.1038/nm.3407 · Cited by 2,452
IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel
Lennon, V. A., Kryzer, T. J., Pittock, S. J., Verkman, A. S., & Hinson, S. R. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050304 · Cited by 2,288
Pericytes are required for blood–brain barrier integrity during embryogenesis
Daneman, R., Zhou, L., Kebede, A. A., & Barres, B. A. (2010) · Nature · doi:10.1038/nature09513 · Cited by 2,128
Kebir, H., Kreymborg, K., Ifergan, I., Dodelet-Devillers, A., Cayrol, R., Bernard, M., Giuliani, F., Arbour, N., Becher, B., & Prat, A. (2007) · Nature Medicine · doi:10.1038/nm1651 · Cited by 1,759
Claudin-based tight junctions are crucial for the mammalian epidermal barrier
Furuse, M., Hata, M., Furuse, K., Yoshida, Y., Haratake, A., Sugitani, Y., Noda, T., Kubo, A., & Tsukita, S. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200110122 · Cited by 1,512
Bell, R. D., Winkler, E. A., Sagare, A. P., Singh, I., LaRue, B., Deane, R., & Zlokovic, B. V. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.043 · Cited by 1,448
A Randomized, Controlled Trial of Corticosteroids in the Treatment of Acute Optic Neuritis
Beck, R. W., Cleary, P. A., Anderson, M. M., Keltner, J. L., Shults, W. T., Kaufman, D. I., Buckley, E. G., Corbett, J. J., Kupersmith, M. J., Miller, N. R., et al. (1992) · New England Journal of Medicine · doi:10.1056/nejm199202273260901 · Cited by 1,349
Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 Signaling
Chung, Y., Chang, S. H., Martínez, G., Yang, X. O., Nurieva, R., Kang, H. S., Ma, L., Watowich, S. S., Jetten, A. M., Tian, Q., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.02.007 · Cited by 1,247
Astrocyte barriers to neurotoxic inflammation
Sofroniew, M. V. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3898 · Cited by 1,202
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Verkhratsky, A., & Butt, A. M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-821565-4.00005-5
Abadey, A. A. (2023) · Open Access Victoria University of Wellington | Te Herenga Waka (Figshare) · doi:10.26686/wgtn.23639313
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Correale, J. D., & Marrodán, M. (2024) · Springer eBooks · doi:10.1007/978-3-031-24297-7_10-1
Correale, J. D., & Marrodán, M. (2024) · Springer eBooks · doi:10.1007/978-3-031-60006-7_10
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Colomer, T., Sánchez-Martín, E., Bernal‐Chico, A., Moreno‐García, A., Serrat, R., Baraibar, A. M., Uribe-Irusta, A., Iriarte-Sarria, A., Skupio, U., Matute, C., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.23.660998
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Lu, X., Yan, R., & Song, S. (2025) · Academia Medicine and Health · doi:10.20935/acadmedhealth7977
Duan, M., Ru, X., Zhou, J., Li, Y., Guo, P., Kang, W., Li, W., Chen, Z., Feng, H., & Chen, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26721699
Duan, M., Ru, X., Zhou, J., Li, Y., Guo, P., Kang, W., Li, W., Chen, Z., Feng, H., & Chen, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26721696
Church, K. A., Rodriguez, D., Vanegas, D., Gutiérrez, I. L., Cardona, S. M., Madrigal, J. L. M., Kaur, T., & Cardona, A. E. (2023) · Figshare · doi:10.6084/m9.figshare.22611893
The effect of astrocyte depletion and repopulation approaches in pathological condition of CNS
Tahmasebi, F., Safarian, A., Asl, E. R., Vahidinia, Z., & Barati, S. (2026) · Acta Neurologica Belgica · doi:10.1007/s13760-026-03005-z
Salvioni, A. (2018) · theses.fr (ABES) · doi:10.70675/1822c41bzc1afz45a7z8f3dzc8d2bdd4e272
Lebas, H. (2018) · theses.fr (ABES) · doi:10.70675/50d09d4bzd5d4z462bz974ez3b3e69f504e6
Leventoux, N. (2018) · theses.fr (ABES) · doi:10.70675/1b8ddd02z3a93z40cdz9da9z8c69201d9db7
Contribution de la voie Wnt dans la stabilité de la barrière hémato-encéphalique
Gueniot, F. (2019) · theses.fr (ABES) · doi:10.70675/7bb4438cz6983z40a4zb67bzd7cc0b7bb81c
Rethinking MS Therapeutics: From Disease Pathogenesis Mechanisms to AI-Driven Drug Discovery
Ziaei, M., Sehhati, M., Torabi, M., Esmaeil, N., & Ghasemi, F. (2026) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-026-10286-x
Glioma microenvironment: Cellular crosstalk, immunosuppression, and novel therapeutic perspectives
Hu, Y., Liang, J., Xu, J., & Zhao, L. (2026) · Chinese Medical Journal · doi:10.1097/cm9.0000000000004151
Kumar, D., Kalpina, F., Saif, I., Shujaat, T., Rizvi, S. M. A., Mohsin, M. S., Kumar, S., Teena, F., Javeid, J., Inam, S. H. A., et al. (2026) · Journal of the National Medical Association · doi:10.1016/j.jnma.2026.06.012
Yi, L., Yang, L., Wang, K., Liu, H., Chen, R., Su, M., Xiao, X., & Zhang, Y. (2026) · Advanced Science · doi:10.1002/advs.76932
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Sadaqa, E., & Hanafy, A. S. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.115323
Metadata
- Authors
- Horng, S., Therattil, A., Moyon, S., Gordon, A., Kim, K., Argaw, A. T., Hara, Y., Mariani, J. N., Sawai, S., Flodby, P., Crandall, E. D., Borok, Z., Sofroniew, M. V., Chapouly, C., & John, G. R.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- University of Southern California (US)
- University of California, Los Angeles (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2017-07-24
- Volume
- 127
- Issue
- 8
- Pages
- 3136-3151
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5531407
- OpenAlex
- W2737157719
- Cited by
- 221
- References
- 69
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 21 · 2023: 29 · 2022: 26 · 2021: 34 · 2020: 26 · 2019: 23 · 2018: 29 · 2017: 3
- FWCI
- 11.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL AMU (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Icahn School of Medicine at Mount Sinai
- Guthy-Jackson Charitable Foundation
- Hastings Foundation
- Beker Foundation
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL119165, R01HL126877, U01HL108634, R01HL112638)
- National Cancer Institute (R24CA095823)
- National Institute of Neurological Disorders and Stroke (R01NS062703, R25NS079102, R01NS084030, R01NS085103)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- glia limitans, multiple sclerosis, blood-brain barrier, claudin-4, claudin-1, JAM-A, reactive astrocytes, leukocyte transmigration, neuroinflammation, motor impairment
- MeSH terms
- Animals, Astrocytes, Blood-Brain Barrier, Central Nervous System, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Inflammation, Mice, Inbred C57BL, Multiple Sclerosis, Nervous System Diseases, Receptors, Cell Surface, Cell Adhesion Molecules, Cytokines, Mice, Knockout, Coculture Techniques, Tight Junctions, Mice, Claudin-1, Claudin-4
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