T cells in multiple sclerosis and experimental autoimmune encephalomyelitis

Fletcher, Jean M.; Lalor, Stephen J.; Sweeney, Cheryl; Tubridy, Niall; Mills, Kingston H. G.

doi:10.1111/j.1365-2249.2010.04143.x

Cited by 787 publications

(652 citation statements)

References 118 publications

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“…This is in accordance with the proposed regulatory role of CD8 + cells in EAE. 22 Eosinophilic leukocytes were observed in infiltrates of R8316 (IL-5)-treated EAE mice, but were also observed in the other EAE groups in accordance with observations in other EAE models 52 (Supplementary Figure 1).…”

Section: Discussionsupporting

confidence: 86%

“…20,21 CD8 + T cells may also have a regulatory role in EAE. 22 Evidence suggests that Th2 type cytokines, such as IL-4 and IL-10 are associated with the recovery phase of EAE and also of MS, 23 whereas certain cytokines such as IFN-g, tumor necrosis factor-a and tumor necrosis factor-b have a disease-promoting role. 24 The Th1/Th2 paradigm in autoimmune disease has been targeted for potential treatments of EAE.…”

Section: Multiple Sclerosis (Ms) Is a Demyelinating Autoimmune Diseasmentioning

confidence: 99%

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Treatment of experimental autoimmune encephalomyelitis in SJL/J mice with a replicative HSV-1 vector expressing interleukin-5

et al. 2011

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Experimental autoimmune encephalomyelitis (EAE) is an autoimmune inflammation of the central nervous system and is used as the experimental model of multiple sclerosis (MS). The exact mechanism behind the disease is still unknown, but interleukin (IL)-17 expressing T cells are thought to mediate the disease. Toll-like receptors (TLRs) are known to have a role in the innate immune response against pathogens, and several TLRs have also a role in the disease course of EAE. Here, we show that treatment with a herpes simplex virus type 1 vector expressing the Th2 cytokine IL-5 ameliorates EAE and decreases the numbers of infiltrating lymphocytes in the brain. The effect involves downregulation of TLR 2, 3 and 9 mRNA expression and upregulation of type I interferons (IFNs) in brains during onset of disease. The elevated expression of type I IFNs was also observed during recovery.

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Section: Discussionsupporting

confidence: 86%

Section: Multiple Sclerosis (Ms) Is a Demyelinating Autoimmune Diseasmentioning

confidence: 99%

Treatment of experimental autoimmune encephalomyelitis in SJL/J mice with a replicative HSV-1 vector expressing interleukin-5

et al. 2011

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“…Both IFN-c-secreting T H 1 cells and IL-17-secreting T H 17 cells are associated with activation of encephalitogenic T-cells, CNS inflammation, and demyelinating lesions (Wang et al 2006;Fletcher et al 2010;Lovett-Racke et al 2011;Rostami & Ciric 2013). T H 2/T reg cellrelated cytokines like IL-4, IL-10, and TGF-b have been shown to be associated with reductions in inflammation and improvement of symptoms in MS patients (Oreja-Guevara et al 2012;Koutrolos et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Haghmorad

Salehipour

Nosratabadi

et al. 2016

Journal of Immunotoxicology

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Estrogen is a neuro-protective hormone in various central nervous system (CNS) disorders. The present study evaluated the role of estrogen during experimental autoimmune encephalomyelitis (EAE) at doses selected to mimic any suppressive potential from the hormone during pregnancy. Here, mice were ovariectomized and then 2 weeks later treated with MOG antigen to induce EAE. Concurrently, mice then received (subcutaneously) an implanted pellet to deliver varying estrogen amounts over a 21-day period. Clinical scores and other parameters were monitored daily for the 21 days. At the end of the period, brain/spinal cord histology was performed to measure lymphocyte infiltration; T-cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed using real-time PCR; T-cell differentiation was evaluated via flow cytometry. The results demonstrated that estrogen inhibited development of EAE. Histological studies revealed limited leukocyte infiltration into the CNS. High and medium dose of estrogen increased T H 2 and T reg cell production of interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-b, but concurrently resulted in a significant reduction in production of interferon (IFN)-c, IL-17, and IL-6. Flow cytometry revealed there were also significant decreases in the percentages of T H 1 and T H 17 cells, as well as significant increase in percentages of T reg and T H 2 cells in the spleen and lymph nodes. Real-time PCR results indicated that high-and medium-dose estrogen treatments reduced T-bet and ROR-ct factor expression, but enhanced Foxp3 and GATA3 expression. Collectively, these results demonstrated that a medium dose of estrogen -similar to a pregnancy level of estrogen -could potentially reduce the incidence and severity of autoimmune EAE and possibly other autoimmune pathologies.ARTICLE HISTORY

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“…The EAE is driven, in principle, by the proinflammatory cytokines IL-17 and IFN-γ, and resolved by the anti-inflammatory cytokines TGF-β and IL-10 [27]. Therefore, we examined the effects of TCDD treatment on these cytokines in encephalitogenic LN CD4 + cells restimulated with MOG .…”

Section: Tcdd-induced Cholinergic Anti-inflammation Suppresses Il-17mentioning

confidence: 99%

MicroRNA‐132 suppresses autoimmune encephalomyelitis by inducing cholinergic anti‐inflammation: A new Ahr‐based exploration

Hanieh

Abdullah

2013

Eur J Immunol

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MicroRNAs (miRNAs) are a small group of RNAs that are emerging as a new avenue by which autoimmune diseases may be modulated. Accumulating evidence shows that miRNAs are involved in the pathogenesis of MS; however, the interaction of miRNAs with environmentally responsive transcription factors that play prominent roles in MS is unexplored. The activation of aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) alleviates inflammation in experimental autoimmune encephalomyelitis (EAE), the best available model of MS. Therefore, we predicted that TCDD could attenuate EAE by inducing miRNA(s) targeting inflammatory mediators. Here, we show that TCDD induces cholinergic anti-inflammation in EAE mice by upregulating acetylcholinesterasetargeting miR-132. The expression of miR-132 was downregulated in CD4 + cells and associated with EAE severity, while TCDD treatment attenuated EAE by inducing the miR-132/acetylcholinesterase module. Silencing miR-132 in vivo abolished TCDDinduced cholinergic anti-inflammation and aggravated EAE. Overexpression of miR-132 in encephalitogenic CD4 + cells decreased IL-17 and IFN-γ and suppressed T-cell proliferation. In conclusion, our findings identify a new miRNA-based mechanism through which miR-132 mediates TCDD-induced EAE attenuation, suggesting that miR-132 could be a promising therapeutic target for anti-inflammatory treatment of MS.Keywords: Ahr r Cholinergic anti-inflammation r EAE · MicroRNA r miR-132 r TCDD Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionThe aryl hydrocarbon receptor (Ahr) is a ligand-dependent transcription factor activated by a long list of exogenous ligands including 2,3,7, [1] and 3-methylcholanthrene [2]. Ahr has been shown to mediate the mechanisms that underlie environmental and immunotoxicity [3]. Therefore, Ahr represents a fascinating link between the environment and the immune system. Previously, we and others have Correspondence: Dr. Hanieh Hamza e-mail: hhanieh@kfu.edu.sa demonstrated that Ahr is implicated in the differentiation of Th17/Treg cells [4][5][6], development of autoimmunity [7], and secretion of proinflammatory cytokines [8,9]. Importantly, activation of Ahr has shown a therapeutic potential for autoimmune inflammation. For example, TCDD mitigates CNS inflammation in experimental autoimmune encephalomyelitis (EAE) [5], an established animal model of MS. However, the toxicity of TCDD prohibits its clinical application, and therefore, mechanistic explanation of TCDD-attenuated inflammation may open intriguing possibilities for applicable treatment of MS in human.The microRNAs (miRNAs) are small endogenous noncoding RNAs of ∼22 nt that post-transcriptionally regulate gene expression. These molecules are implicated in different aspects of C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Hanieh Hamza and Alzahrani AbdullahEur. J. Immunol. 2013Immunol. . 43: 2771Immunol. -2782 inflammation. For instance, miR-155, miR-146a, a...

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T cells in multiple sclerosis and experimental autoimmune encephalomyelitis

Cited by 787 publications

References 118 publications

Treatment of experimental autoimmune encephalomyelitis in SJL/J mice with a replicative HSV-1 vector expressing interleukin-5

Treatment of experimental autoimmune encephalomyelitis in SJL/J mice with a replicative HSV-1 vector expressing interleukin-5

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

MicroRNA‐132 suppresses autoimmune encephalomyelitis by inducing cholinergic anti‐inflammation: A new Ahr‐based exploration

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