Suppression of ongoing experimental autoimmune myasthenia gravis by transfer of RelB-silenced bone marrow dentritic cells is associated with a change from a T helper Th17/Th1 to a Th2 and FoxP3+ regulatory T-cell profile

Yang, Huan; Zhang, Yong; Wu, Minghua; Li, Jing; Zhou, Weiping; Li, Guiyuan; Li, Xiaoling; Xiao, Bo; Christadoss, Premkumar

doi:10.1007/s00011-009-0087-6

Cited by 41 publications

(34 citation statements)

References 54 publications

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“…Also, the proliferative response of T cells in response to AChR stimulation was increased when stimulated by IL-17 in vitro [64e66]. Moreover, treatment with immunosuppressive bone marrow stromal cells or dendritic cells ameliorated EAMG symptoms by shifting the balance from Th1/Th17 dominance towards Th2/Treg dominance [65,66]. A similar balance between regulatory and inflammatory T cells was also observed in a clinical study, in which MG patients with reduced Treg cells showed more severe MG symptoms [67].…”

Section: Th1/th17 Versus Th2-type Immunitymentioning

confidence: 99%

“…Intravenous injection of RelB-silenced dendritic cells to B6 mice with established EAMG effectively reduced muscle weakness. This effect was associated with a shift from Th1/Th17 to a Th2 and regulatory T cell profile [65]. Moreover, administration of granulocyteemacrophage colony stimulating factor (GM-CSF), a growth factor promoting anti-inflammatory dendritic cell production, before or after EAMG induction resulted in decreased EAMG incidence and severity in B6 mice [71].…”

Section: Dendritic Cell Manipulation As a Treatment Modelmentioning

confidence: 99%

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Complement and cytokine based therapeutic strategies in myasthenia gravis

Tüzün

Huda

Christadoss

2011

Journal of Autoimmunity

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Section: Th1/th17 Versus Th2-type Immunitymentioning

confidence: 99%

Section: Dendritic Cell Manipulation As a Treatment Modelmentioning

confidence: 99%

Complement and cytokine based therapeutic strategies in myasthenia gravis

Tüzün

Huda

Christadoss

2011

Journal of Autoimmunity

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“…All of these proteins have been knocked out in mice, and deficiency of RelB or a combined deficiency of RelA and p50 or c-Rel and p50 all result in DC loss (22,23). The noncanonical transcription factor RelB has further been shown to have a critical role in DC maturation and immunogenicity (22,(24)(25)(26)(27). Canonical NF-kB activation, which involves phosphorylation and subsequent degradation of the inhibitory IkB proteins enabling nuclear translocation of RelA, c-Rel, and/or p50 dimers, has also been associated with activationinduced DC maturation and function (28)(29)(30)(31).…”

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confidence: 99%

A Nonredundant Role for Canonical NF-κB in Human Myeloid Dendritic Cell Development and Function

Laar

Bosch

Kooij

et al. 2010

The Journal of Immunology

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The plastic role of dendritic cells (DCs) in the regulation of immune responses has made them interesting targets for immunotherapy, but also for pathogens or tumors to evade immunity. Functional alterations of DCs are often ascribed to manipulation of canonical NF-κB activity. However, though this pathway has been linked to murine myeloid DC biology, a detailed analysis of its importance in human myeloid DC differentiation, survival, maturation, and function is lacking. The myeloid DC subsets include interstitial DCs and Langerhans cells. In this study, we investigated the role of canonical NF-κB in human myeloid DCs generated from monocytes (monocyte-derived DCs [mo-DCs]) or CD34+ progenitors (CD34-derived myeloid DCs [CD34-mDCs]). Inhibition of NF-κB activation during and after mo-DC, CD34-interstitial DC, or CD34-Langerhans cell differentiation resulted in apoptosis induction associated with caspase 3 activation and loss of mitochondrial transmembrane potential. Besides regulating survival, canonical NF-κB activity was required for the acquisition of a DC phenotype. Despite phenotypic differences, however, Ag uptake, costimulatory molecule and CCR7 expression, as well as T cell stimulatory capacity of cells generated under NF-κB inhibition were comparable to control DCs, indicating that canonical NF-κB activity during differentiation is redundant for the development of functional APCs. However, both mo-DC and CD34-mDC functionality were reduced by NF-κB inhibition during activation. In conclusion, canonical NF-κB activity is essential for the development and function of mo-DCs as well as CD34-mDCs. Insight into the role of this pathway may help in understanding how pathogens and tumors escape immunity and aid in developing novel treatment strategies aiming to interfere with human immune responses.

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“…The efficacy of this treatment is due to the activation of specific DC subpopulations and expansion of the regulatory T-cell compartment (Sheng et al 2006). Finally, recent data demonstrate that the administration of bone marrow DC, RelB-silenced and pulsed with Ta146-162, is able to suppress EAMG progression in mice, by inducing a positive shift in favour of Th2/regulatory T cell responses (Yang et al 2010).…”

Section: Induction Of Peripheral Tolerancementioning

confidence: 99%

Acetylcholine Receptor-Induced Experimental Myasthenia Gravis: What Have We Learned from Animal Models After Three Decades?

Baggi

Antozzi

Toscani

et al. 2011

Arch. Immunol. Ther. Exp.

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Myasthenia gravis (MG) is an autoimmune disease caused by an immunological response against the acetylcholine receptor (AChR) at the neuromuscular junction. Anti-AChR antibodies induce degradation of the receptor, activation of complement cascade and destruction of the post-synaptic membrane, resulting in a functional reduction of AChR availability. The pathophysiological role of autoantibodies (auto-Abs) and T helper lymphocytes has been studied in the experimental autoimmune MG (EAMG) models. EAMG models have been employed to investigate the factors involved in the development of MG and to suggest new therapies aimed to preventing or modulating the ongoing disease. EAMG can be induced in susceptible mouse and rat strains, which develop clinical symptoms such as muscular weakness and fatigability, mimicking the human disease. Two major types of EAMG can be induced, passive and active EAMG. Passive transfer MG models, involving the injection of auto-Abs, are helpful for studying the role of complement molecules and their regulatory proteins, which can prevent neuromuscular junction degradation. Active models, induced by immunization, are employed for the analysis of antigen-specific immune responses and their modulation in order to improve disease progression. In this review, we will concentrate on the main pathogenic mechanisms of MG, focusing on recent findings on EAMG experimental models.

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Suppression of ongoing experimental autoimmune myasthenia gravis by transfer of RelB-silenced bone marrow dentritic cells is associated with a change from a T helper Th17/Th1 to a Th2 and FoxP3+ regulatory T-cell profile

Cited by 41 publications

References 54 publications

Complement and cytokine based therapeutic strategies in myasthenia gravis

Complement and cytokine based therapeutic strategies in myasthenia gravis

A Nonredundant Role for Canonical NF-κB in Human Myeloid Dendritic Cell Development and Function

Acetylcholine Receptor-Induced Experimental Myasthenia Gravis: What Have We Learned from Animal Models After Three Decades?

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