Cited by 297Multiple Sclerosis Research StudiesPsoriasis: Treatment and PathogenesisT-cell and B-cell Immunology

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Astrocyte-Restricted Ablation of Interleukin-17-Induced Act1-Mediated Signaling Ameliorates Autoimmune Encephalomyelitis

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Kang, Zizhen, Altuntas, Cengiz Zubeyir, Gulen, Muhammet Fatih, Liu, Caini, Giltiay, Natalia, Qin, Hongwei, Liu, Liping, Qian, Wen, Ransohoff, Richard M., Bergmann, Cornelia, Stohlman, Stephen, Tuohy, Vincent K., Li, Xiaoxia·2010·Immunity

DOI 10.1016/j.immuni.2010.03.004PMC PMC3073618

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Abstract

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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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: Kang, Zizhen
Gulen, Muhammet Fatih
Liu, Caini
Giltiay, Natalia
Ransohoff, Richard M.
Bergmann, Cornelia
Tuohy, Vincent K.
Li, Xiaoxia
Venue: Immunity
Publisher: Elsevier BV
Published: 2010-03
Volume: 32
Issue: 3
Pages: 414-425
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2010.03.004
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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Astrocyte-Restricted Ablation of Interleukin-17-Induced Act1-Mediated Signaling Ameliorates Autoimmune Encephalomyelitis

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