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Acute T-cell-mediated rejection of the renal allograft is a serious posttransplant challenge that requires administration of high-dose immunosuppressive drugs with considerable side effects; therefore, specific targeting of T-cell responses may improve both prevention and treatment of T-cell-mediated rejection. A potential candidate for this purpose is interferon regulatory factor 4 because of its implication in differentiation and function of T cells. Our aim was to evaluate the frequency of the rs872071AG and rs12203592CT single-nucleotide polymorphisms of the interferon regulatory factor 4 gene and association of these 2 polymorphisms with the gene expression of programmed cell death 1 and Helios in patients with T-cell-mediated rejection versus stable recipients.Sixty recipients with T-cell- mediated rejection and 60 age-matched and sex-matched stable recipients were recruited. Two single-nucleotide polymorphisms of interferon regulatory factor 4 gene, as well as the expression of programmed cell death 1 and Helios genes in peripheral blood mononuclear cells, were investigated with real-time polymerase chain reaction.Programmed cell death 1 gene expression was reduced in patients with T-cell-mediated rejection versus stable recipients (P = .03). The frequency of rs872071AG and rs12203592CT single-nucleotide polymorphisms showed no significant difference between groups. Presence of the rs12203592CT single-nucleotide polymorphism was directly correlated with the expression of programmed cell death 1 gene (P = .049), and rs872071AG positivity was directly correlated with Helios gene expression (P = .008), which suggests an inhibitory role for interferon regulatory factor 4 on programmed cell death 1 and Helios molecules.Programmed cell death 1 gene expression was lower in patients with T-cell-mediated rejection versus stable recipients. Low-expressing singlenucleotide polymorphisms of interferon regulatory factor 4 could enhance the downstream gene expression of programmed cell death 1 and Helios immunoregulatory molecules. Therefore, specific inhibition of interferon regulatory factor 4 may promote tolerance induction in the allograft.

The major current focus on treating rheumatoid arthritis is to put an end to long-term treatments and instead, specifically block widespread immunosuppression by developing antigen-specific tolerance, while also permitting an intact immune response toward other antigens to occur. There have been promising preclinical findings regarding adoptive Treg cells immunotherapy with a critically responsible function in the prevention of autoimmunity, tissue repair and regeneration, which make them an attractive candidate to develop effective therapeutic approaches to achieve this interesting concept in many human immune-mediated diseases, such as rheumatoid arthritis. Ex vivo or invivo manipulation protocols are not only utilized to correct Treg cells defect, but also to benefit from their specific immunosuppressive properties by identifying specific antigens that are expressed in the inflamedjoint. The methods able to address these deficiencies can be considered as a target for immunity interventions to restore appropriate immune function.

Particulate matter (PM) as the carcinogenic air pollutants can lead to aggravated health outcomes. Epidemiological studies demonstrated that PM can be engaged in different diseases such as cardiovascular, respiratory and cancer. The in vitro secretion of proinflammatory cytokines by human peripheral blood mononuclear cells (PBMCs) has been used to assess the effects of PM with an aerodynamic diameter

Laboratory and epidemiological researches have indicated that ambient air particulate matter have a plays critical role in causing diseases. The current research evaluated the chemical attributes of PM2.5 in the ambient air of the cities of Karaj and Fardis and determined its toxicological effects on human lung epithelial cells (A549). In the study city, 16 points were selected from the two high-traffic and low-traffic points for sampling. A sampling of ambient air was carried out in spring, summer, autumn, and winter 2018–19. Air sampling was performed for 24 h according to the EPA-TO/13A guidelines. To analyze of toxic metals and polycyclic aromatic hydrocarbons (PAHs), ICP-OES and GC-MS were used, respectively, and for cell toxicity analysis, an ELISA reader was used. Then from SPSS, Excel and R software were used for statistical analysis. The results of the current study indicated that the concentration of PAHs carcinogenic in the autumn season in high-traffic stations was the highest and equal to 9.3 ng/m(3), and in the spring season in the low-traffic stations, it was the lowest and equal to 5.82 ng/m(3). In general, during the period of study, Heavy metals including Zn, Fe, Pb, Cu, and Al had the highest concentration compared to other metals. However, Hg, Cr, As, Pb, Cu, Cd, and Zn were higher concentration in the winter and autumn seasons than in the spring and summer seasons. Cell viability measurements by using MTT showed that low-traffic and high-traffic stations had the highest toxicity in autumn season compared to other seasons. (p

Renal transplant rejection is one of the clinical challenges, which usually requires administration of immunosuppressive drugs causing serious side effects. Therefore, invention of effective and specific therapeutics is necessary to control undesired immune responses particularly T-cell reactions to allograft. Interferon Regulatory Factor-4 (IRF-4) due to its implication on T cells differentiation and function might be targeted to treat T cell-mediated cellular rejection (TCMR). The aim of this study was to investigate the association between IRF-4 gene expression and acute TCMR, as well as to examine the correlation between IRF-4 gene expression and cellular expression of Programmed cell death-1 (PD-1) and Helios molecules.Peripheral blood samples were obtained from 30 patients with biopsy proven acute TCMR and 30 stable recipients. IRF-4 gene expression was quantified using RT-PCR, and cellular expression of PD-1 and Helios were evaluated with flowcytometry.IRF-4 gene expression was significantly increased in acute TCMR patients compared with stable recipients (P.05). Helios protein expression was slightly decreased in TCMR group but this was not statistically significant. There was a negative correlation between IRF-4 gene expression and PD-1 as well as Helios frequency in the whole studied population.IRF-4 expression increases in acute TCMR which might also lead to a diminished expression of downstream immunoregulatory molecules such as PD-1 and Helios. Therefore, specific inhibition of IRF-4 may be helpful in managing acute TCMR.

Ankylosing spondylitis (AS) is an inflammatory autoimmune disease. AS is a prototype form of spondyloarthropathies (SpA). The precise etiology of AS has not been fully understood. But Inflammation has a critical role in the pathogenesis of the disease. The immune system by various cells, secreted-mediators and markers manage and regulate the immune responses and inflammation. Every factor which disturbed this regulation and hemostasis can cause chronic inflammation. In this review, we discussed the role of several innate and adaptive immune cells involved in the triggering, initiation, development, and regulation of AS.

Graphical abstract, The International Agency for Research on Cancer (IARC) has defined outdoor air pollution and PM as the human carcinogen (Group 1), which mainly cause an increased risk of lung cancer. Scientists have considered epigenetic modifications as a possible mechanism to deal with adverse effects of air pollution. This study aimed to compare the effect of airborne PM10 (PM with aerodynamic diameter ≤10 μm) on in vitro global methylation in human peripheral blood mononuclear cells (PBMCs). PM10 was sampled in metropolitan Tehran, the capital of Iran. PBMCs were extracted from whole blood of healthy males and treated with PM10 suspension at concentrations of 50–300 μg/mL for 4 h. Untreated cells were used as the negative control. Genomic DNA was extracted from each sample using the DNA blood mini kit according to the manufacturer’s instruction. Moreover, 5-methylsytosine (%5-mC) and 5-hydroxymethylcytosine (%5-hmC) were measured by the enzyme-linked immunosorbent assay (ELISA) method. %5-mC and %5-hmC in each sample was compared with negative control and reported as difference %5-mC and %5-hmC.

Sirtuin 1, a member of sirtuin family of histone deacetylase enzymes, has been implicated in a variety of physiologic and pathologic events, including energy metabolism, cell survival, and age-related alterations. In view of the anti-inflammatory properties of sirtuin 1 along with its protective role in ischemia reperfusion injury, it might be considered as contributing to the promotion of transplantation outcome. However, the potential ability of sirtuin 1 to induce malignancies raises some concerns about its overexpression in clinic. Moreover, despite the findings of sirtuin 1 implication in thymic tolerance induction and T regulatory (Treg) cells survival, there is also evidence for its involvement in Treg suppression and in T helper 17 cells differentiation. The identification of sirtuin 1 natural and synthetic activators leads to the proposal of sirtuin 1 as an eligible target for clinical interventions in transplantation. All positive and negative consequences of sirtuin 1 overactivation/overexpression in the allograft should therefore be studied thoroughly. Herein, we summarize previous findings concerning direct and indirect influences of sirtuin 1 manipulation on transplantation.

BackgroundPrimary membranous nephropathy (PMN) is an autoimmune disease affecting renal glomerulus, characterized by autoantibodies aggregation on podocytes and subsequent epithelial thickening. Therefore, rituximab, an anti-CD20 monoclonal antibody, is used to treat patients with the deteriorating condition.ObjectivesAssuming that rituximab demolishes a considerable number of B-lymphocytes and causes transient immunodeficiency, we aimed to identify B cell subsets involved in PMN pathogenesis to facilitate specific targeting.MethodsUsing flowcytometery, 25 PMN patients including 15 on standard treatment and 10 on standard treatment plus rituximab were enrolled to compare with healthy controls. Rituximab-receiving patients were studied before and two months after administration.ResultsNeither total CD19+ nor memory B cell percentages showed significant differences between the study groups. However, the number of B regulatory cells (Breg) was lower in both standard-treatment and Rituximab-receiving patients than in controls. Moreover, the percentage of naive/mature B cells dropped after standard treatment.ConclusionsPMN patients seem to possess an insufficient percentage of Breg cells, which are involved in immunomodulation. Furthermore, the standard-treatment group showed a reduced count of naive/mature B cells, which constitute a substantial proportion of normal B lymphocytes population.

PURPOSE: This study aimed to investigate chemical composition of PM(10) (particulate matter with aerodynamic diameter ≤ 10 μm) during dust storm and inversion in Tehran and hemolysis effects. METHODS: PM(10) was sampled in Tehran, Iran, during dust storm and inversion conditions. Water soluble ions (F¯, Cl¯, NO(2)¯, NO(3)¯, SO(4)¯(2), Na(+), K(+), NH(4)(+), Ca(+2), Mg(+2)) and elements (Al, Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Se, Sn, Sr, V, Zn, Pt, Rh, Pd, As and Si) were analyzed by ion chromatograph (IC) and inductively coupled plasma optical emission spectrometer (ICP-OES), respectively. Hemolysis was examined as in vitro at PM(10) concentrations of 50–300 μg/ml. RESULTS: Daily average of PM(10) concentrations in dusty and inversion days were 348.40 and 220.54 μg/m(3), respectively. Most prevalence ionic components were NO(3)¯, Cl¯, SO(4)¯(2) and Ca(+2) during dust storm and SO(4)¯(2), NO(3)¯, Cl¯ and NH(4)(+) during inversion. Si, Fe and Al had the maximum values in both conditions. Particles associated with both conditions induced hemolytic responses. PM(10) from dusty day showed a higher hemolysis percent (10.24 ± 4.67%) than inversion (9.08 ± 5.47%), but this difference was not significant (p = 0.32). Hemolytic effects were significantly intensified by increased PM concentrations (p

Particulate matter (PM) as the carcinogenic air pollutants can lead to aggravated health outcomes. Epidemiological studies demonstrated that PM can be engaged in different diseases such as cardiovascular, respiratory and cancer. The in vitro secretion of proinflammatory cytokines by human peripheral blood mononuclear cells (PBMCs) has been used to assess the effects of PM with an aerodynamic diameter

Please note that the corresponding author’s correct affiliation is “Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Programmed cell death 1 (PDCD-1, also named PD-1, CD279, and SLEB2), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of autoimmune diseases such as rheumatoid arthritis (RA). Herein, we investigate the association of PDCD-1 polymorphisms with the risk of RA among Iranian patients and healthy controls.Genomic DNA was extracted from the whole blood samples using DNA Purification kit (DNG-plus). Using the PCR- RFLP method, 3 PDCD-1 SNPs, including PD1.1G/A, PD1.3G/A, and PD1.9C/T were genotyped in 120 RA patients as well as 188 healthy controls. The genotype and allele frequencies of these SNPs were analysed by statistical tests for the significant association between RA patients and controls. Haplotype constructions of these SNPs were performed. Clinical diagnosis of the RA patients was confirmed by the Rheumatology Research Centere of Tehran University of Medical Sciences.Our study revealed that PD1.1 A allele at position -538 in the promoter region of PDCD-1 gene is associated with an increased risk of RA disease compared to controls (2.9% vs. 0.7%, OR= 3.735, 95% CI= 0.956-14.588, p=0.046). There were no significant differences in other alleles and genotypes of PDCD-1 SNPs between RA cases and controls.Our results indicate that among the polymorphisms which we evaluated only the PD1.1A allele in the promoter region of PDCD-1 gene is significantly associated with RA susceptibility in Iranian patients.