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Astrocyte-Restricted Ablation of Interleukin-17-Induced Act1-Mediated Signaling Ameliorates Autoimmune Encephalomyelitis
Open accessAbstract
SUMMARY Interleukin-17 (IL-17) secreted by T helper 17 (Th17) cells is essential in the development of experimental autoimmune encephalomyelitis (EAE). However, it remains unclear how IL-17-mediated signaling in different cellular compartments participates in the central nervous system (CNS) inflammatory process. We examined CNS inflammation in mice with specific deletion of Act1, a critical component required for IL-17 signaling, in endothelial cells, macrophages and microglia, and neuroectoderm (neurons, astrocytes, and oligodendrocytes). In Act1-deficient mice, Th17 cells showed normal infiltration into the CNS but failed to recruit lymphocytes, neutrophils, and macrophages. Act1 deficiency in endothelial cells or in macrophages and microglia did not substantially impact the development of EAE. However, targeted Act1 deficiency in neuroectoderm derived CNS resident cells resulted in markedly reduced severity in EAE. Specifically, Act1-deficient astrocytes showed impaired IL-17-mediated inflammatory gene induction. Thus, astroctyes are critical in IL-17-Act1 mediated leukocyte recruitment during autoimmune induced inflammation of the CNS.
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“such as its previously identified actions on astrocytes that may alter astrocyteneuronal interactions (52).”
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Metadata
- Authors
- Kang, Z., Altuntas, C. Z., Gulen, M. F., Liu, C., Giltiay, N., Qin, H., Liu, L., Qian, W., Ransohoff, R. M., Bergmann, C., Stohlman, S., Tuohy, V. K., & Li, X.
- Affiliations
- Cleveland Clinic (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Tuohy, Vincent K.
- Li, Xiaoxia
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 32
- Issue
- 3
- Pages
- 414-425
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3073618
- OpenAlex
- W2026778930
- Semantic Scholar
- f4c926ee0558c380c2f9303d6eee5cc35e0466eb
- Cited by
- 297
- References
- 64
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 15 · 2023: 18 · 2022: 17 · 2021: 25 · 2020: 15 · 2019: 17 · 2018: 15 · 2017: 16 · 2016: 18 · 2015: 21 · 2014: 23 · 2013: 21 · 2012: 29
- FWCI
- 17.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1234 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 AI065470)
- National Multiple Sclerosis Society (RG 4056-A-1)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-17, Act1, experimental autoimmune encephalomyelitis, astrocytes, Th17 cells, neuroinflammation, leukocyte recruitment, endothelial cells, macrophages, microglia, neuroectoderm
- MeSH terms
- Animals, Astrocytes, Cell Survival, Encephalomyelitis, Autoimmune, Experimental, Gene Expression Regulation, T-Lymphocytes, Helper-Inducer, Macrophages, Mice, Inbred C57BL, Signal Transduction, Mice, Knockout, Interleukin-17, Adaptor Proteins, Signal Transducing, Mice
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