Regulatory function of CD4+CD25++ T cells in patients with myasthenia gravis is associated with phenotypic changes and STAT5 signaling: 1,25-Dihydroxyvitamin D3 modulates the suppressor activity

Alahgholi-Hajibehzad, Mahdi; Oflazer, Piraye; Aysal, Fikret; Durmuş, Hacer; Gülşen-Parman, Yeşim; Marx, Alexander; Deymeer, Feza; Saruhan‐Direskeneli, Güher

doi:10.1016/j.jneuroim.2015.03.008

Cited by 35 publications

(40 citation statements)

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“…We did observe an association between 25-vitD levels and the amount of CD4 + CD25 +high PD-1 + T cells at baseline, but this association was not sustained by oral vitamin D or placebo treatment. The TCR- stimulation induced PD1-uregulation in CD4 + T cells was more pronounced in CD than in HC, which is line with previous findings in patients with other chronic inflammatory diseases than CD [24, 30]. …”

Section: Discussionsupporting

confidence: 92%

Vitamin D increases programmed death receptor-1 expression in Crohn’s disease

et al. 2017

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Background: Vitamin D modulates inflammation in Crohns disease (CD). Programmed death (PD)-1 receptor contributes to the maintenance of immune tolerance. Vitamin D might modulate PD-1 signalling in CD.Aim: To investigate PD-1 expression on T cell subsets in CD patients treated with vitamin D or placebo.Methods: We included 40 CD patients who received 1200 IU vitamin D3 for 26 weeks or placebo and eight healthy controls. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated at baseline and week 26. The expressions of PD-1, PD-L1, and surface activation markers were analysed by flow cytometry. Soluble PD-1 plasma levels were measured by ELISA.Results: PD-1 expression upon T cell stimulation was increased in CD4+CD25+int T cells in vitamin D treated CD patients from 19% (range 10 39%) to 29% (11 79%)(p = 0.03) compared with placebo-treated patients. Vitamin D treatment, but not placebo, decreased the expression of the T cell activation marker CD69 from 42% (31 62%) to 33% (19 - 54%)(p = 0.01). Soluble PD-1 levels were not influenced by vitamin D treatment.Conclusions: Vitamin D treatment increases CD4+CD25+int T cells ability to up-regulate PD-1 in response to activation and reduces the CD69 expression in CD patients.

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Section: Discussionsupporting

confidence: 92%

Vitamin D increases programmed death receptor-1 expression in Crohn’s disease

et al. 2017

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“…CD4 + CD25 + FoxP3 + regulatory T cells have a key role in controlling autoimmunity and maintaining immunologic selftolerance [105]. Recent studies have reported functional defects of CD4 + CD25 + regulatory T cells from thymuses of MG patients and reduction in peripheral regulatory T cell population in untreated MG patients [106][107][108][109][110][111][112]. Impairment of suppressive activity of regulatory T cells and reduction in frequency of regulatory T cells in the spleen and peripheral blood were also demonstrated in EAMG rats [113,114].…”

Section: Mechanisms Of Specific Immunotherapymentioning

confidence: 99%

AChR-specific immunosuppressive therapy of myasthenia gravis

Luo

Lindstrom

2015

Biochemical Pharmacology

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“…The transcription factor FoxP3 is selectively expressed in Tregs, which is the key modulators of Tregs activation and function (Marson et al, 2007). Tregs actively mediate self-tolerance and thus control autoimmunity by suppressing the activation, proliferation, and effector function such as a cytokine production of various immune cells (Sakaguchi et al, 2008; Alahgholi-Hajibehzad et al, 2015b). Conversely, Th17 cells play a crucial role in the initiation and maintenance of autoimmune tissue injury (Schaffert et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Chinese Herbal Medicine for Myasthenia Gravis: A Systematic Review and Meta-Analysis

Chen

Zhou

et al. 2018

Front. Pharmacol.

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Myasthenia gravis (MG) is an acquired autoimmune disease with the disorder of the neuromuscular junction transmission caused by autoantibodies. Currently, various Chinese herbal medicines (CHMs) are widely used for MG. This meta-analysis was conducted to assess the effectiveness and safety of CHMs for MG and its possible mechanisms. Fourteen studies with 1039 individuals were identified by searching seven databases from inception to March 2017. The methodological quality was assessed by using 7-item criteria from the Cochrane’s Collaboration tool, and which assessed ≥4 “yes” in the domains were selected for detailed assessment and meta-analysis. All the data were analyzed using Rev-Man 5.3 software. Meta-analysis showed a significant effect of CHM as adjuvant therapy for improving the effectiveness compared with WCM alone or placebo in treating MG (p < 0.01). Moreover, there were fewer adverse effects and relapse rate in total when compared with the control group. The possible mechanisms of CHM for MG are associated with immunoregulation by reconstituting the functional ability of Tregs. In conclusion, despite the apparent positive results, the present evidence supports, to an extent, that CHM can be used for MG patients because of the methodological flaws and CHM heterogeneity. Further rigorous RCT for MG is needed.

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Regulatory function of CD4+CD25++ T cells in patients with myasthenia gravis is associated with phenotypic changes and STAT5 signaling: 1,25-Dihydroxyvitamin D3 modulates the suppressor activity

Cited by 35 publications

References 48 publications

Vitamin D increases programmed death receptor-1 expression in Crohn’s disease

Vitamin D increases programmed death receptor-1 expression in Crohn’s disease

AChR-specific immunosuppressive therapy of myasthenia gravis

Chinese Herbal Medicine for Myasthenia Gravis: A Systematic Review and Meta-Analysis

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