Circulating Levels of Interleukin-35 in Patients with Multiple Sclerosis: Evaluation of the Influences of FOXP3 Gene Polymorphism and Treatment Program

Jafarzadeh, Abdollah; Jamali, Mitra; Mahdavi, Roya; Ebrahimi, Hossein Ali; Hajghani, Hossain; Khosravimashizi, Arezu; Nemati, Maryam; Najafipour, Hamid; Sheikhi, Abdolkarim; Mohammadi, Mohammad Mahdi; Daneshvar, Hamid

doi:10.1007/s12031-014-0443-z

Cited by 74 publications

(51 citation statements)

References 27 publications

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“…Another study demonstrated that the frequency AA and AC genotypes of rs3761548 are significantly higher in MS patients than healthy subjects (29). Another study in a South India population reported that C alleles in rs3761548 are associated with susceptibility to pre-eclampsia (30); nevertheless, these two studies are inconsistent with our results.…”

Section: Discussioncontrasting

confidence: 93%

Functional Genetic Variants of FOXP3 and Risk of Multiple Sclerosis

Gholami

Darvish

Ahmadi

et al. 2016

Iran Red Crescent Med J

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Background: Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS). MS is one of the most common cause of neurological impairment at a young age with a complex etiology. The forkhead/winged helix (FOXP3) gene encodes a transcription factor that plays an important role in the working and progress of regulatory T cells. Loss of the FOXP3 function impairs the suppressor activity of regulatory T (T-reg) cells, which have been reported in MS patients. Objectives: To determine whether rs2232365 and rs3761548 polymorphisms of FOXP3 are associated with the risk of MS in an Iranian population. Patients and Methods:In this case-control study, a total of 384 samples consisting of 190 MS patients and 194 unrelated healthy subjects from the Iranian population were recruited between December 2014 and September 2015. The patients were diagnosed by a neurologist based on McDonald's criteria. The control group had no history or presence of autoimmune diseases. The polymorphisms were genotyped using tetra-ARMS PCR and PCR-restriction fragment length polymorphism (RFLP) techniques. Results: The Rs2232365 G allele was significantly associated with an increased risk of MS (P = 0.0068). In contrast, the allele and genotype frequencies of rs3761548 was not significantly different between the case and control groups (P > 0.05). Conclusions:The functional variant of the FOXP3, rs2232365 A/G, may be considered a substantial risk factor for MS.

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Section: Discussioncontrasting

confidence: 93%

Functional Genetic Variants of FOXP3 and Risk of Multiple Sclerosis

Gholami

Darvish

Ahmadi

et al. 2016

Iran Red Crescent Med J

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“…14,15 The former are generated from precursor cells in the thymus, whereas antigenic stimulation in the presence of TGF-β and IL-2 causes differentiation of naïve CD4 + T cells into the latter cells in the peripheral lymphoid organs. 14,15 Indeed, lower levels of TGF-β have been reported among patients with HT, potentially accounting for their decreased FOXP3 expression. 34 The findings of the present study suggest that the downregulation of Treg cell-related functions may contribute to HT pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 Treg cells play a protective role against thyroid autoimmune diseases, with Treg cell depletion shown to promote experimental autoimmune thyroiditis in mice. 16,17 A balanced ratio of Th1/Th2, Th1/Treg, Th2/Treg and Th17/Treg cells is required for normal immune function; as such, imbalances in effector T cell functioning have been associated with a number of autoimmune diseases.…”

mentioning

confidence: 99%

Imbalances in T Cell-Related Transcription Factors Among Patients with Hashimoto’s Thyroiditis

Safdari¹,

Alijani²,

Nemati³

et al. 2017

SQUMJ

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abstract:Objectives: Imbalances in effector T cell functioning have been associated with a number of autoimmune diseases, including Hashimoto's thyroiditis (HT). Differentiation of effector T helper (Th) 1, Th2, Th17 and regulatory T cell (Treg) lymphocytes is regulated by transcription factors, including Th1-specific T box (T-bet), GATA binding protein-3 (GATA 3 ), retinoid-related orphan receptor (ROR)-α and forkhead box P3 (FOXP3). This study aimed to investigate Th1/Th2, Th1/Treg, Th2/Treg and Th17/Treg balances at the level of these transcription factors. Methods: This study took place between October 2015 and August 2016. Peripheral blood mononuclear cells were collected from a control group of 40 healthy women recruited from the Zahedan University of Medical Sciences, Zahedan, Iran, and a patient group of 40 women with HT referred to the Hazrat Ali Asghar Hospital, Zahedan. Total ribonucleic acid extraction was performed and the gene expression of transcription factors was quantitated using a real-time polymerase chain reaction technique. Results: Expression of T-bet and GATA 3 was significantly elevated, while FOXP3 expression was significantly diminished among HT patients in comparison with the controls (P = 0.03, 0.01 and 0.05, respectively). Expression of RORα was higher among HT patients, although this difference was not significant (P = 0.15). Expression of T-bet/FOXP3, GATA 3 /FOXP3 and RORα/FOXP3 ratios were increased among HT patients in comparison with the controls (P <0.02, <0.01 and <0.01, respectively). Conclusion: These results indicate that HT patients have imbalances in Th1/Treg, Th2/Treg and Th17/Treg lymphocytes at the level of the transcription factors, deviating towards Th1, Th2 and Th17 cells. Correction of these imbalances may therefore be therapeutic. Keywords

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“…The role of Th2 cells, which secrete high levels of IL-4, IL-5, and IL-13, remains controversial (Raphael et al 2015). We have previously observed the elevated concentrations of a Th17-related chemokine (CCL20), diminished levels of a Th2/Treg-related chemokine (CCL22), and unchanged levels of a Treg-related cytokine in patients with MS (Jafarzadeh et al 2014a;Jafarzadeh et al 2014b;Jafarzadeh et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Altered Expression of Specific Transcription Factors of Th17 (RORγt, RORα) and Treg Lymphocytes (FOXP3) by Peripheral Blood Mononuclear Cells from Patients with Multiple Sclerosis

et al. 2016

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The imbalance in Th17/Treg cell-related responses plays an important role in the pathogenesis of multiple sclerosis (MS). The development of Th17- and Treg cells is regulated by specific transcription factors-RORγt and RORα-and FOXP3, respectively. The aim was to determine the expression of RORγt, RORα, and FOXP3 in peripheral blood mononuclear cells (PBMCs) from MS patients following in vitro stimulation. The PBMCs from 22 MS patients and 20 healthy subjects were cultured in the presence of 10 μg/ml MOG, 10 μg/ml PHA, or without stimulation. The PBMCs were incubated at 37 °C for 24 h, and then the messenger RNA (mRNA) expression of RORγt, RORα, and FOXP3 was determined by real-time PCR. The expression of RORγt and RORα was increased in non-stimulated, MOG-stimulated, and PHA-stimulated PBMCs from MS patients in comparison with same cultures from the healthy group (P < 0.01, P < 0.01, and P < 0.02 for RORγt; P < 0.001, P < 0.001, and P < 0.05, for RORα, respectively). The FOXP3 expression in non-stimulated PBMCs from MS patients was significantly lower than that in equal culture from healthy subjects (P < 0.05). There were no significant differences between healthy subjects and MS patients regarding the expression of FOXP3 mRNA by MOG-stimulated and PHA-stimulated PBMCs. These results showed an imbalance in Th17/Treg cells at transcription factor levels with a deviation toward Th17 cell in MS. The correction of Th17/Treg balance at transcription levels should be considered to design novel therapeutic strategies for MS treatment.

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Circulating Levels of Interleukin-35 in Patients with Multiple Sclerosis: Evaluation of the Influences of FOXP3 Gene Polymorphism and Treatment Program

Cited by 74 publications

References 27 publications

Functional Genetic Variants of FOXP3 and Risk of Multiple Sclerosis

Functional Genetic Variants of FOXP3 and Risk of Multiple Sclerosis

Imbalances in T Cell-Related Transcription Factors Among Patients with Hashimoto’s Thyroiditis

Altered Expression of Specific Transcription Factors of Th17 (RORγt, RORα) and Treg Lymphocytes (FOXP3) by Peripheral Blood Mononuclear Cells from Patients with Multiple Sclerosis

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