Peptide immunotherapy in experimental autoimmune encephalomyelitis

Anderton, Stephen M.

doi:10.4103/2319-4170.158510

Cited by 12 publications

(10 citation statements)

References 91 publications

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“…In addition to the anti-inflammatory effect of AA3 shown in the present study, the previously demonstrated neuroprotective and cognition-enhancing effects of AA3 [ 21 ] may provide additional benefit to patients with MS, because cognitive impairment is a common clinical feature in both the earlier and later phases of the disease [ 37 ]. Because of the complex nature of the pathogenesis of MS and neurodegeneration in general, multifunctional drugs with both neuroprotective and anti-inflammatory properties, such as AA3, are attracting significant attention in drug development for MS. New therapeutic strategies for MS, including immunological tolerance induction [ 38 – 40 ], cell-based therapy [ 41 , 42 ], microbiota therapies [ 43 ], blood—brain barrier protection [ 44 , 45 ], and demyelination prevention [ 46 , 47 ] have recently been validated experimentally and clinically. Accordingly, it is of interest to determine if AA3 exhibits effects beyond the effects of the abovementioned novel treatment approaches for MS.…”

Section: Discussionmentioning

confidence: 99%

Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response

et al. 2017

PLoS ONE

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Anemoside A3 (AA3) is a natural triterpenoid glycoside isolated from the root of Pulsatilla chinensis (Bunge) Regel. We previously showed that AA3 exhibits cognitive-enhancing and neuroprotective properties. In the present study, we demonstrated that AA3 modulates inflammatory responses by regulating prostaglandin E receptor 4 signaling. Because prostaglandin E receptor 4 is involved in the pathophysiology of experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), we assessed the beneficial effect of AA3 in EAE mice. AA3 treatment significantly reduced clinical severity and inflammatory infiltrates in the spinal cord of EAE mice. In vitro studies revealed that AA3 inhibited the T cell response toward the encephalitogenic epitope of myelin oligodendrocyte glycoprotein (MOG). AA3 significantly downregulated the expressions of certain Th1 and Th17 cytokines in activated T cells re-stimulated by MOG. Moreover, AA3 inhibited the activation of STAT4 and STAT3, which are the transcription factors pivotal for Th1 and Th17 lineage differentiation, respectively, in activated T cells. Pharmacological analysis further suggested that AA3 reduced Th17 cell differentiation and expansion. In conclusion, AA3 exerts an immunomodulatory effect in EAE, demonstrating its potential as a therapeutic agent for MS in humans.

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Section: Discussionmentioning

confidence: 99%

Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response

et al. 2017

PLoS ONE

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“…Administration of specific encephalitogenic antigens by various routes, including mucosal, i.v., i.p., s.c. and oral, can induce immune tolerance in EAE [7, 23, 24]. DCs, as professional APCs, can be induced into a tolerogenic phenotype, with the ability to promote the function of regulatory T cells or inhibit activation of autoreactive T cells [25–27].…”

Section: Discussionmentioning

confidence: 99%

Selective depletion of CD11c⁺CD11b⁺ dendritic cells partially abrogates tolerogenic effects of intravenous MOG in murine EAE

Wang

Ćirić

et al. 2016

Eur J Immunol

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Intravenous (i.v.) injection of a soluble myelin antigen can induce tolerance, which effectively ameliorates experimental autoimmune encephalomyelitis (EAE). We have previously shown that i.v. MOG induces tolerance in EAE and expands a subpopulation of tolerogenic CD11c+CD11b+ dendritic cells (DCs) with an immature phenotype having low expression of IA and co-stimulatory molecules CD40, CD86, and CD80. Here we further investigate the role of tolerogenic DCs in i.v. tolerance by injecting clodronate-loaded liposomes, which selectively deplete CD11c+CD11b+ and immature DCs, but not CD11c+CD8+ DCs and mature DCs. I.v. MOG-induced suppression of EAE was partially, yet significantly, blocked by CD11c+CD11b+ DC depletion. While i.v. MOG inhibited IA, CD40, CD80, CD86 expression and induced TGF-β, IL-27, IL-10 production in CD11c+CD11b+ DCs, these effects were abrogated after injection of clodronate-loaded liposomes. Depletion of CD11c+CD11b+ DCs also precluded i.v. autoantigen-induced T-cell tolerance, such as decreased production of IL-2, IFN-γ, IL-17 and numbers of IL-2+, IFN-γ+, and IL-17+ CD4+ T cells, as well as an increased proportion of CD4+CD25+Foxp3+ regulatory T cells and CD4+IL-10+Foxp3− Tr1 cells. CD11c+CD11b+ DCs, through low expression of IA and co-stimulatory molecules as well as high expression of TGF-β, IL-27 and IL-10, play an important role in i.v. tolerance-induced EAE suppression.

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“…DC, dendritic cells; LT, lymphocyte T; LB, lymphocyte T; Mϕ, macrophage. may therefore be exploited for diseases in which dysfunction of the same host immune reactions is implicated in their pathogenesis, for instance the innate immune system in Sjögren's syndrome (42), adaptive immunity in Tregopathies (43) and autoimmune encephalomyelitis (44), and complement activation in local and/or systemic inflammation, tissue damage, and disease (45).…”

Section: Impact Of Tick Salivary Compounds On Host Immune Responsesmentioning

confidence: 99%

Tick Salivary Compounds for Targeted Immunomodulatory Therapy

et al. 2020

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Immunodeficiency disorders and autoimmune diseases are common, but a lack of effective targeted drugs and the side-effects of existing drugs have stimulated interest in finding therapeutic alternatives. Naturally derived substances are a recognized source of novel drugs, and tick saliva is increasingly recognized as a rich source of bioactive molecules with specific functions. Ticks use their saliva to overcome the innate and adaptive host immune systems. Their saliva is a rich cocktail of molecules including proteins, peptides, lipid derivatives, and recently discovered non-coding RNAs that inhibit or modulate vertebrate immune reactions. A number of tick saliva and/or salivary gland molecules have been characterized and shown to be promising candidates for drug development for vertebrate immune diseases. However, further validation of these molecules at the molecular, cellular, and organism levels is now required to progress lead candidates to clinical testing. In this paper, we review the data on the immunopharmacological aspects of tick salivary compounds characterized in vitro and/or in vivo and present recent findings on non-coding RNAs that might be exploitable as immunomodulatory therapies.

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Peptide immunotherapy in experimental autoimmune encephalomyelitis

Cited by 12 publications

References 91 publications

Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response

Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response

Selective depletion of CD11c⁺CD11b⁺ dendritic cells partially abrogates tolerogenic effects of intravenous MOG in murine EAE

Tick Salivary Compounds for Targeted Immunomodulatory Therapy

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Peptide immunotherapy in experimental autoimmune encephalomyelitis

Cited by 12 publications

References 91 publications

Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response

Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response

Selective depletion of CD11c+CD11b+ dendritic cells partially abrogates tolerogenic effects of intravenous MOG in murine EAE

Tick Salivary Compounds for Targeted Immunomodulatory Therapy

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Selective depletion of CD11c⁺CD11b⁺ dendritic cells partially abrogates tolerogenic effects of intravenous MOG in murine EAE