Early Life Exposure to Lipopolysaccharide Suppresses Experimental Autoimmune Encephalomyelitis by Promoting Tolerogenic Dendritic Cells and Regulatory T Cells

Ellestad, Kristofor K.; Tsutsui, Shigeki; Noorbakhsh, Farshid; Warren, Kenneth G.; Yong, V. Wee; Pittman, Quentin J.; Power, Christopher

doi:10.4049/jimmunol.0803576

Cited by 59 publications

(59 citation statements)

References 39 publications

(46 reference statements)

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“…Frontal brain white matter was collected at autopsy with consent from ageand sex-matched MS patients (total: n = 8; median age: 63 y; chronic progressive MS: n = 3; secondary progressive MS: n = 5) and non-MS (control) patients (total: n = 7; median age: 58 y; sepsis: n = 2; myocardial infarction: n = 2; HIV/AIDS: n = 1: cancer/leukemia n = 2) for RT-PCR analyses, as previously reported (32)(33)(34). Normal-appearing white matter (NAWM) was used from all clinical samples.…”

Section: Human Brain Tissue Samplesmentioning

confidence: 99%

“…starting at day 7 post-EAE induction, whereas control EAE animals received daily i.p. PBS (32)(33)(34). Crocin prevents oligodendrocyte cytotoxicity induced by supernatants from astrocytes overexpressing Syncytin-1.…”

Section: Induction and Assessment Of Eaementioning

confidence: 99%

“…Ab (16-0031-86; eBioscience) at 10 mg/ml with or without 100 mM crocin (17304; Sigma) (34). For myelin oligodendrocyte glycoprotein (MOG)-specific proliferation assay, splenocytes were isolated from EAE-induced mice at peak of disease and were cultured in the presence of 20 mg/ml MOG peptide (prepared by the Peptide Synthesis Facility, University of Calgary) with or without 100 mM crocin.…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

“…Control animals were only injected with CFA and pertussis toxin. Animals were assessed daily for EAE severity for 25 d using a 0-14 rating scale (34). EAE mice received crocin (100 mg/kg/d; Sigma-Aldrich) daily and i.p.…”

Section: Induction and Assessment Of Eaementioning

confidence: 99%

“…Anti-CD3ε Ab was used with compbeads (552845; BD Biosciences) for single-color compensation controls. The total percentage (%) of the CD3ε + T lymphocyte proliferation population was analyzed using FlowJo (Tree Star software) (34).…”

Section: Flow Cytometrymentioning

confidence: 99%

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Neuroinflammation and Endoplasmic Reticulum Stress Are Coregulated by Crocin To Prevent Demyelination and Neurodegeneration

Deslauriers

Afkhami-Goli

Paul

et al. 2011

The Journal of Immunology

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112

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Endoplasmic reticulum (ER) stress is a homeostatic mechanism, which is used by cells to adapt to intercellular and intracellular changes. Moreover, ER stress is closely linked to inflammatory pathways. We hypothesized that ER stress is an integral component of neuroinflammation and contributes to the development of neurological diseases. In autopsied brain specimens from multiple sclerosis (MS) and non-MS patients, XBP-1 spliced variant (XBP-1/s) was increased in MS brains (p < 0.05) and was correlated with the expression of the human endogenous retrovirus-W envelope transcript, which encodes the glycoprotein, Syncytin-1 (p < 0.05). In primary human fetal astrocytes transfected with a Syncytin-1–expressing plasmid, XBP-1/s, BiP, and NOS2 were induced, which was suppressed by crocin treatment (p < 0.05). Crocin also protected oligodendrocytes exposed to cytotoxic supernatants derived from Syncytin-1–expressing astrocytes (p < 0.05) and NO-mediated oligodendrocytotoxicity (p < 0.05). During experimental autoimmune encephalomyelitis (EAE), the transcript levels of the ER stress genes XBP-1/s, BiP, PERK, and CHOP were increased in diseased spinal cords compared with healthy littermates (p < 0.05), although CHOP expression was not involved in the EAE disease phenotype. Daily treatment with crocin starting on day 7 post-EAE induction suppressed ER stress and inflammatory gene expression in spinal cords (p < 0.05), which was accompanied by preserved myelination and axonal density, together with reduced T cell infiltration and macrophage activation. EAE-associated neurobehavioral deficits were also ameliorated by crocin treatment (p < 0.05). These findings underscored the convergent roles of pathogenic ER stress and immune pathways in neuroinflammatory disease and point to potential therapeutic applications for crocin.

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Section: Human Brain Tissue Samplesmentioning

confidence: 99%

Section: Induction and Assessment Of Eaementioning

confidence: 99%

Section: Cell Proliferation Assaymentioning

confidence: 99%

Section: Induction and Assessment Of Eaementioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

See 3 more Smart Citations

Neuroinflammation and Endoplasmic Reticulum Stress Are Coregulated by Crocin To Prevent Demyelination and Neurodegeneration

Deslauriers

Afkhami-Goli

Paul

et al. 2011

The Journal of Immunology

Self Cite

112

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Neuromyelitis Optica With Extensive Active Brain Involvement

Almekhlafi¹,

Clark²,

Lucchinetti³

et al. 2011

Arch Neurol

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IL‐10 deficiency blocks the ability of LPS to regulate expression of tolerance‐related molecules on dendritic cells

Zhou

Ćirić

et al. 2012

Eur J Immunol

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Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays an important role in regulating the local inflammatory immune response, but regulatory mechanisms of this cytokine have not been fully elucidated. Here, we demonstrate that IL-10 deficiency renders LPS treatment ineffective in regulating the expression of CD40, CD80, CD86, B7-H2, and B7-DC on dendritic cells (DCs) and blocks upregulation of IL-27. This inability to respond to LPS was found in both IL-10−/− bone marrow derived and splenic DCs. Compared with wild-type DCs, IL-10−/− DCs expressed similar levels of TLR4 and CD14, but produced less LPS-binding protein. The deficiency in LPS-binding protein production may explain the failure of IL-10−/− DCs to respond normally to LPS.Moreover, lack of IL-10 modulated the proportions of CD11c+CD8+ and CD11c+B220+ DCs, which play an important role in local inflammatory responses and tolerance. IL-10 deficiency also blocked expression of galectin-1, CD205, and CD103, which are necessary for central and peripheral tolerance. While they did not respond to LPS, IL-10−/− DCs produced increased levels of IL-6 and CCL4 after TNF-α treatment. Together, our results demonstrate that IL-10 deficiency affects the immune functions of DCs, which may contribute to the increased severity of autoimmune diseases seen in IL-10−/− mice.

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Early Life Exposure to Lipopolysaccharide Suppresses Experimental Autoimmune Encephalomyelitis by Promoting Tolerogenic Dendritic Cells and Regulatory T Cells

Cited by 59 publications

References 39 publications

Neuroinflammation and Endoplasmic Reticulum Stress Are Coregulated by Crocin To Prevent Demyelination and Neurodegeneration

Neuroinflammation and Endoplasmic Reticulum Stress Are Coregulated by Crocin To Prevent Demyelination and Neurodegeneration

Neuromyelitis Optica With Extensive Active Brain Involvement

IL‐10 deficiency blocks the ability of LPS to regulate expression of tolerance‐related molecules on dendritic cells

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