Journal article
Astrocyte-Restricted Ablation of Interleukin-17-Induced Act1-Mediated Signaling Ameliorates Autoimmune Encephalomyelitis
Immunity (Cambridge, Mass.), Vol.32(3), pp.414-425
2010
DOI: 10.1016/j.immuni.2010.03.004
PMCID: PMC3073618
PMID: 20303295
Abstract
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.
► Th17 cell-mediated leukocyte infiltration was attenuated in Act1-deficient CNS ► Act1 in endothelial cells, macrophage, and microglia was dispensable for EAE ► Act1 deficiency in neuroectoderm resulted in markedly reduced severity in EAE ► IL-17-dependent cytokines and chemokines in astrocytes are critical for EAE
Details
- Title: Subtitle
- Astrocyte-Restricted Ablation of Interleukin-17-Induced Act1-Mediated Signaling Ameliorates Autoimmune Encephalomyelitis
- Creators
- Zizhen Kang - Cleveland ClinicCengiz Zubeyir Altuntas - Cleveland ClinicMuhammet Fatih Gulen - Cleveland ClinicCaini Liu - Cleveland ClinicNatalia Giltiay - Cleveland ClinicHongwei Qin - University of Alabama at BirminghamLiping Liu - Cleveland ClinicWen Qian - Cleveland ClinicRichard M Ransohoff - Cleveland ClinicCornelia Bergmann - Cleveland ClinicStephen Stohlman - Cleveland ClinicVincent K Tuohy - Cleveland ClinicXiaoxia Li - Cleveland Clinic
- Resource Type
- Journal article
- Publication Details
- Immunity (Cambridge, Mass.), Vol.32(3), pp.414-425
- DOI
- 10.1016/j.immuni.2010.03.004
- PMID
- 20303295
- PMCID
- PMC3073618
- NLM abbreviation
- Immunity
- ISSN
- 1074-7613
- eISSN
- 1097-4180
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2010
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984201120102771
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