Th17 Cell, the New Player of Neuroinflammatory Process in Multiple Sclerosis

Jadidi‐Niaragh, Farhad; Mirshafiey, Abbas

doi:10.1111/j.1365-3083.2011.02536.x

Cited by 331 publications

(221 citation statements)

References 166 publications

(233 reference statements)

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“…Modulation of the activation of human pDCs, induced by CCK8, might provide novel immune-based targets for therapies in autoimmunity and transplantation. CCK8 may therefore be involved in modulation of immune responses to prevent immunological overdrive and promote maintenance of immune tolerance, which could have substantial implications for the treatment of Th1-dominated and/or Th17-dominated autoimmune diseases [33][34][35]. Our study confirms that the CCK system is involved in the CpG DNA-induced expression or phosphorylation of IRF5, IRF7, and TRAF6, which are all essential steps in the activation of pDCs.…”

Section: Discussionsupporting

confidence: 71%

CCK8 negatively regulates the TLR9‐induced activation of human peripheral blood pDCs by targeting TRAF6 signaling

et al. 2013

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Plasmacytoid dendritic cells (pDCs) are specialized in rapid and massive secretion of type I interferon in response to foreign nuclei acids. Combined with their antigen presentation capacity, this powerful functionality enables pDCs to orchestrate innate and adaptive immune responses. Cholecystokinin octapeptide (CCK8) is a potent immunomodulator, whose role in pDCs function is unknown. In this study, we found that two different cholecystokinin receptors, CCK1R and CCK2R, are expressed on human peripheral blood pDCs. Exogenous CCK8 was able to modulate the TLR-induced activation of pDCs, including phenotypic maturation, IFN-α synthesis and secretion, and could also regulate the potential of pDCs to induce adaptive immune responses in vitro. CCK8 inhibited TLR9-induced activation of tumor-necrosis factor receptor-associated factor 6, which is an important adapter protein in activation of interferon-regulatory factor (IRF)5 and IRF7, possibly through CCK2R, by evoking the activity of protein kinase (PK)A and reducing the activity of PKC. All these results indicate that CCK8 can inhibit the TLR9-induced phenotypic maturation and activation of pDCs, acting through CCK2R by modulating the tumor-necrosis factor receptor-associated factor 6 signaling pathways. Keywords: CCK8 · IFN-α · IRF7 · Plasmacytoid dendritic cells · TRAF6Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionTwo naturally occurring DC types have been described in human peripheral blood: plasmacytoid dendritic cells (pDCs)/professional type I interferon-producing cells and classical dendritic cells (cDCs)/myeloid DCs [1,2]. pDCs are considered the main sentinels against viral infections and play a major role in immune tolerance [3]. This function of pDCs is linked to their expression of TLR7 and TLR9, both of which sense viral nucleic acids within the early endosomes [4,5]. TLR9 is only expressed by Correspondence: Prof. Bin Cong e-mail: hbydbincong@126.com pDCs in the human setting and is responsible for a very high type I IFN response. Tumor necrosis factor-associated factor 6 (TRAF6) is critical for mediating TLR signaling and subsequent activation of interferon-regulatory factor (IRF) 5 and IRF7, transcriptional activators of innate immunity [6].An increasing amount of data supports the idea that the nervous, endocrine, and immune systems are closely interconnected and that they mutually influence their respective functions through common mediators and receptors. It is known that some neuropeptides, namely vasoactive intestinal peptide and somatostatin, inhibit the proliferative response of lymphocytes [7,8]. Members of the cholecystokinin (CCK)/gastrin family of peptides play an important role in the regulation of feeding behavior and energy homeostasis [9]. CCK is identified as several different forms C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 490Xianxian Jia et al. Eur. J. Immunol. 2014. 44: 489-499 of the peptide with different sizes, includ...

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Section: Discussionsupporting

confidence: 71%

CCK8 negatively regulates the TLR9‐induced activation of human peripheral blood pDCs by targeting TRAF6 signaling

et al. 2013

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“…The role of Th17 cells (a subset of T cells that produce a distinct profile of proinflammatory cytokines, including interleukin [IL]-17, IL-6, IL-9, IL-21, IL-22, IL-23, IL-26 and tumour necrosis factor-α [TNF-α]) in the immunopathogenesis of MS and EAE has recently been elucidated [28][29][30]. GA was found to reduce Th-17-related neuroinflammation and levels of IL-17 and IL-6 in EAE mice [31,32].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

The heritage of glatiramer acetate and its use in multiple sclerosis

Comı

Amato

Bertolotto

et al. 2016

Mult Scler Demyelinating Disord

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Multiple sclerosis (MS) is a chronic and progressively debilitating disease of the central nervous system. Treatment of MS involves disease-modifying therapies (DMTs) to reduce the incidence of relapses and prevent disease progression. Glatiramer acetate (Copaxone®) was the first of the currently approved DMTs to be tested in human subjects, and it is still considered a standard choice for first-line treatment. The mechanism of action of glatiramer acetate appears to be relatively complex and has not been completely elucidated, but it is likely that it involves both immunomodulating and neuroprotective properties. The efficacy of glatiramer acetate 20 mg/mL once daily as first-line treatment in relapsingremitting MS is well established, with ample evidence of efficacy from both placebo-controlled and active-comparator controlled clinical trials as well as real-world studies. There is also a considerable body of evidence indicating that the efficacy of glatiramer acetate is maintained in the long term. Clinical trial and real-world data have also consistently shown glatiramer acetate to be safe and well tolerated. Notably, glatiramer acetate has a good safety profile in women planning a pregnancy, and is not associated with foetal toxicity. Until recently, glatiramer acetate was only approved as 20 mg/mL once daily, but a new formulation with less frequent administration, 40 mg/mL three times weekly, has been developed and is now approved in many countries, including Italy. This review examines the mechanism of action, clinical efficacy, safety and tolerability of glatiramer acetate to provide suggestions for optimizing the use of this drug in the current MS therapeutic scenario.

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“…The production of IL-6 and IL-17 is involved in MS development (27). IL-17, by degradation of BBB, causes demyelination and neuroinfl ammation (28). Astaxanthin by inhibiting ROS, can reduce infl ammatory mediators in arthritis (29).…”

Section: Discussionmentioning

confidence: 99%

Astaxanthin effectiveness in preventing multiple sclerosis in animal model

Bidaran¹,

Ahmadi²,

Yaghmaei³

et al. 2018

BLL

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OBJECTIVE: The aim of the present study was to reveal the effect of therapeutic and prophylactic potential of astaxanthin in experimental autoimmune encephalomyelitis (EAE) as an acceptable model for the study of multiple sclerosis (MS). BACKGROUND: Astaxanthin has powerful antioxidant activities as well as several essential biological functions while multiple sclerosis prevention is highly regarded by researchers. METHODS: The astaxanthin potential in prevention of multiple sclerosis was examined in the chronic model of experimental autoimmune encephalomyelitis (EAE) by using female C57BL/6 mice induced with oligodendrocyte glycoprotein (MOG). Splenocytes were assessed to measure the levels of proinfl ammatory and antiinfl ammatory cytokines, proliferation rate and FoxP3+Treg cell frequency. Immunohistochemical examinations were performed on spinal cord and brain tissue. RESULTS: Astaxanthin reduced splenocytes proliferation index and proinfl ammatory cytokine levels, and vice versa increased the anti-infl ammatory cytokine levels. Immunohistochemical studies of the spinal cord and brain showed that the infi ltration with infl ammatory cells was highly confi ned in the central nervous system. Protective effects of astaxanthin were visible by assigning low score recording in clinical behavior and disease severity. CONCLUSION: Astaxanthin is a powerful tool for intervention in EAE on a model of multiple sclerosis, so it can be studied further to prevent and treat MS (Tab. 2, Fig. 3, Ref. 41). Text in PDF www.elis.sk.

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Th17 Cell, the New Player of Neuroinflammatory Process in Multiple Sclerosis

Cited by 331 publications

References 166 publications

CCK8 negatively regulates the TLR9‐induced activation of human peripheral blood pDCs by targeting TRAF6 signaling

CCK8 negatively regulates the TLR9‐induced activation of human peripheral blood pDCs by targeting TRAF6 signaling

The heritage of glatiramer acetate and its use in multiple sclerosis

Astaxanthin effectiveness in preventing multiple sclerosis in animal model

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