High doses of α-galactosylceramide potentiate experimental autoimmune encephalomyelitis by directly enhancing Th17 response

Qian, Gaochao; Qin, Xia; Zang, Ying; Ge, Baoxue; Guo, Taylor B.; Wan, Bing; Fang, Lei; Zhang, Jingwu Z.

doi:10.1038/cr.2010.6

Cited by 17 publications

(14 citation statements)

References 42 publications

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“…67,70,76 One study compared subcutaneous versus intraperitoneal a-GalCer administration and found that only subcutaneous administration effectively protected against EAE in this model, 68 although this was not confirmed in a separate study. 67,77 One study further reported that very high doses of a-GalCer (5 lg per animal) exacerbate rather than ameliorate EAE, 77 which is also discordant with some other studies. 67,70 In PL/J mice immunized with myelin basic protein (MBP), a co-treatment protocol similarly ameliorated disease.…”

Section: Effects Of Inkt Cell Activation On Eaesupporting

confidence: 62%

“…These findings are therefore consistent with the previously identified role of IFN-c in the protective effects of a-GalCer against EAE. 77,78 Because MDSCs can give rise to mature myeloid cells, an appealing possibility is that the immunosuppressive DCs and M2 macrophages that accumulate in response to a-GalCer treatment during EAE induction are derived from splenic MDSCs.…”

Section: Effects Of Inkt Cell Activation On Eaementioning

confidence: 99%

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Natural killer T cells in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis

Kaer

Parekh

2015

Immunology

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SummaryMultiple sclerosis (MS) is a chronic inflammatory disease that causes demyelination of neurons in the central nervous system. Traditional therapies for MS have involved anti-inflammatory and immunosuppressive drugs with significant side effects that often only provide short-term relief. A more desirable outcome of immunotherapy would be to protect against disease before its clinical manifestation or to halt disease after its initiation. One attractive approach to accomplish this goal would be to restore tolerance by targeting immunoregulatory cell networks. Although much of the work in this area has focused on CD4 These studies have provided a strong foundation for the rational design of NKT-cell-based immunotherapies for MS that induce tolerance while sparing overall immune function. Nevertheless, additional pre-clinical and clinical studies will be required to bring this goal to fruition.

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Section: Effects Of Inkt Cell Activation On Eaesupporting

confidence: 62%

Section: Effects Of Inkt Cell Activation On Eaementioning

confidence: 99%

Natural killer T cells in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis

Kaer

Parekh

2015

Immunology

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“…It has been shown that repetitive injection of αGalCer can protect mice against EAE (44)(45)(46)(47). Importantly, a single injection of αGalCer did not protect mice against EAE according to most (45,(48)(49)(50), albeit not all (45,50), reports. Differences were attributed to the genetic background, the route and timing of application, and the dosage of αGalCer (45,46,50).…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, a single injection of αGalCer did not protect mice against EAE according to most (45,(48)(49)(50), albeit not all (45,50), reports. Differences were attributed to the genetic background, the route and timing of application, and the dosage of αGalCer (45,46,50). The protection was originally thought to be due to a Th2 bias in the secondary response of αGalCer-pretreated iNKT cells (8,9,62,63).…”

Section: Discussionmentioning

confidence: 99%

IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset

Sağ¹,

Krause²,

Hedrick³

et al. 2014

J. Clin. Invest.

226

269

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“…GalCer can strongly activate iNKT cells to produce immunoregulatory cytokines, including interferon (IFN)-γ, interleukin (IL)- 4, and IL-17, and thereby exert a variety of subsequent effects on other cells in the immune system2. Recent studies have shown the mechanism of GalCer-induced iNKT cell activation in immune responses to tumors and microbes, and in the suppression of autoimmune diseases3456.…”

mentioning

confidence: 99%

Toll-like Receptor agonists and alpha-galactosylceramide synergistically enhance the production of interferon-gamma in murine splenocytes

Ando

Ito

Ohtaki

et al. 2013

Sci Rep

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Vα14 natural killer T (iNKT) cells activated by alpha-galactosylceramide (GalCer) secrete a large amount of cytokines. Toll-like receptors (TLRs) play a critical role in the innate immune responses via the recognition of pathological antigen. Previously we demonstrated that the iNKT cells activated by GalCer augmented LPS-induced NO production in peritoneal cells. In this study, we examined the effect of GalCer and TLR agonists by IFN-γ production from splenocytes. Splenocytes pretreated with GalCer induced TLR3, 4, 7/8, and 9 agonists in vitro, resulting in the enhancement of IFN-γ mRNA expression. In particular, IFN-γ stimulated by GalCer and LPS was increased in NK cells and CD8 T cells, and inhibited by a neutralizing anti-IL-12 antibody. Pretreatment with GalCer enhanced the phosphorylation of IκB-α induced by LPS stimulation. The present study showed that co-stimulation of GalCer and TLR agonists powerfully induced the production of IFN-γ from splenocytes.

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High doses of α-galactosylceramide potentiate experimental autoimmune encephalomyelitis by directly enhancing Th17 response

Cited by 17 publications

References 42 publications

Natural killer T cells in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis

Natural killer T cells in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis

IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset

Toll-like Receptor agonists and alpha-galactosylceramide synergistically enhance the production of interferon-gamma in murine splenocytes

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