Interleukin-2 Expression Levels Research Articles

Targeting the aryl hydrocarbon receptor with FICZ regulates IL-2 and immune infiltration to alleviate Hashimoto's thyroiditis in mice

Hashimoto's thyroiditis (HT) is the most frequent autoimmune disorder. Growing work points to the involvement of aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, in the regulation of immune homeostasis. However, the roles of AhR and its ligands in HT remains unclear. In this study, we leveraged public human database analyses to postulate that the AhR expression was predominantly in thyroid follicular cells, correlating significantly with the thyroid infiltration levels of multiple immune cells in HT patients. Using a thyroglobulin-induced HT mouse model and in vitro thyroid follicular epithelial cell cultures, we found a significant downregulation of AhR expression in thyrocytes both in vivo and in vitro. Conversely, activating AhR by FICZ, a natural AhR ligand, mitigated inflammation and apoptosis in thyrocytes in vitro and conferred protection against HT in mice. RNA sequencing (RNA-seq) of thyroid tissues indicated that AhR activation moderated HT-associated immune or inflammatory signatures. Further, immunoinfiltration analysis indicated that AhR activation regulated immune cell infiltration in the thyroid of HT mice, such as suppressing cytotoxic CD8+ T cell infiltration and promoting anti-inflammatory M2 macrophage polarization. Concomitantly, the expression levels of interleukin-2 (IL-2), a lymphokine that downregulates immune responses, were typically decreased in HT but restored upon AhR activation. In silico validation substantiated the binding interaction between AhR and IL-2. In conclusion, targeting the AhR with FICZ regulates IL-2 and immune infiltration to alleviate experimental HT, shedding new light on the therapeutic intervention of this prevalent disease.

The Diagnostic Value of Combined Detection of Serum Lp-PLA2 and Hcy and Color Doppler in Elderly Patients with Acute Coronary Syndrome and Effect on Endothelial Function.

Objective To evaluate the application value of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and homocysteine (Hcy) combined with color Doppler detection in elderly patients with acute coronary syndrome (ACS) and the influence on their endothelial function. Methods From February 2019 to October 2020, 100 elderly patients with suspected ACS treated in our hospital were recruited and assigned (1 : 1) to a control group or an experimental group. The control group received color Doppler detection, and the experimental group received the combined detection of serum Lp-PLA2 and Hcy and color Doppler. Positive results were determined by the combined detection of the levels of LP-PLA2 and Hcy and color Doppler. The two groups were compared in terms of specificity, susceptibility, positive detection rate, negative detection rate, test accuracy, the area under the receiver operating characteristic (ROC) curve (AUC), the expression levels of interleukin-2 (IL-2), interleukin-12 (IL-12), interleukin-13 (IL-13), and the vascular endothelial function. The patients with ACS were divided into three subgroups according to the Gensini score three-quartile interval, and their Lp-PLA2 levels were calculated for analysis. Results The test specificity, susceptibility, positive detection rate, negative detection rate, test accuracy, and AUC in the experimental group were much better than the those in the control group (all P < 0.05), and there were no significant differences in the expression levels of IL-2, IL-12, IL-13, and vascular endothelial function between the two groups (P > 0.05). The three subgroups showed similar levels of fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, apolipoprotein A-I, glutamic-pyruvic transaminase, lutamic-oxaloacetic transaminase, homocysteine, and amino-terminal pro-brain natriuretic peptide (all P > 0.05). The severe condition group had the highest Lp-PLA2 level, followed by the moderate group, and then the mild group (P < 0.05). Moreover, the levels of LP-PLA2, aspartate transaminase (AST), and N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) were all influencing factors for the coronary Gensini score (all P < 0.05). Conclusion The combined detection of serum Lp-PLA2, Hcy, and color Doppler significantly improves the diagnostic accuracy, specificity, and susceptibility in the elderly with ACS, with little impact on their vascular endothelial function.

Thermal stress consequences on growth performance, immunological response, antioxidant status, and profitability of finishing broilers: transcriptomic profile change of stress-related genes

The current study was conducted to investigate the impact of thermal stress on growth performance, blood biomarkers, metabolic hormones, immunological response, antioxidant activity, and expression of stress-related genes in broilers. One hundred and fifty one-day-old chicks (Ross 308) were utilized in this work. On the 21st day of age, birds were subjected to three environmentally controlled treatments with five replicate pens of 10 birds per each, representing an initial density of 10 birds/m2-control: reared in a thermoneutral condition; THS1 and THS2: exposed to 4 and 6h of daily thermal stress at 40 ± 1°C, respectively, until the 42days of age. The results demonstrated that thermal stress for 4 and 6h significantly reduced (P < 0.001) daily weight gain, daily feed intake, blood leukocyte and lymphocyte counts, serum immunoglobulins (IgM, IgA, IgG), and insulin-like growth factor-1 (IGF-1), while serum levels of aspartate aminotransferase, alanine aminotransferase, glucose, cholesterol, low-density lipoprotein, and lactate dehydrogenase were elevated relative to the thermoneutral group. Additionally, the corticosterone level and the ratio of heterophil:lymphocyte increased significantly (P < 0.001) in thermal-stressed groups. The antioxidant enzymes were affected by thermal stress as represented by a significant decrease in the activity of serum catalase (CAT) and glutathione peroxidase (GSH-Px) along with an increase in malonaldehyde concentration. Thermal stress affected gene expression by upregulating heat shock protein 70, heat shock factors 1 and 3, nuclear factor kappa B, interleukin-4, and uncoupling protein, and downregulating GSH-Px, CAT, and IGF-1 transcript levels. However, no changes were observed in interleukin-2 expression levels. It can be concluded that thermal stress destructively influences productivity, physiological status, and gene expression by upregulating heat shock protein 70, heat shock factors 1 and 3, nuclear factor kappa B, interleukin-4, and uncoupling protein, and downregulating GSH-Px, CAT, and IGF-1 transcript levels of broiler chickens.

Assessment of Interleukin 2 Cytokine Expression Levels After Renal Transplantation

AimEnd-stage renal disease is a disease in which the kidney is not able to perform its functions. Kidney transplantation is the most effective treatment and cost-effective modality of renal replacement therapy for patients with end-stage renal disease. However, the most important problem in end-stage renal disease patients is the unpredictability of immunologic response after transplants. In this study, it was aimed to investigate the possible association between the interleukin 2 (IL-2) expression level and an organ rejection or rejection episode. Materials and MethodsLymphocytes were isolated from peripheral blood obtained from 21 end-stage renal disease–diagnosed patients prior to transplant and at the sixth month after transplant. CD4+ T cells were separated from lymphocytes by the magnetic cell-sorting method. The purity of these cells were controlled by a flow cytometer. After total RNA isolation from CD4+ T cells, IL-2 was examined by the real-time polymerase chain reaction (RT-PCR) method. ResultsAmong nonrejection patients (n = 18), the IL-2 expression level decreased in 12 patients in post-transplant time, and 3 of these were statistically significant (P < .05). The level was the same in 1 of 18 patients; it increased in 5 patients, and 1 of them was significant (P < .05). The IL-2 expression level also increased in 3 patients who had a rejection episode, and the increase was statistically significant in 2 samples (P < .05). ConclusionWhen the patients were evaluated individually, it was observed that there might be a relationship between IL-2 expression levels in CD4+ T cells and rejection episodes. The clinical data of the patients, the immunosuppressive therapies, and post-transplant evaluation of cytokines should be considered together.

Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with cisplatin, inhibits growth of lung cancer cells through transforming growth factor-β1 signaling pathway

ObjectiveTo investigate the tumor inhibition effect of Yangfei Kongliu Formula (YKF), a compound Chinese herbal medicine, combined with cisplatin (DDP) and its action mechanisms. MethodsC57BL/6 mice with Lewis lung carcinoma were divided into six groups: control group (C), DDP group (2 mg/kg, DDP), low-dose YKF group (2.43 g/kg, L), high-dose YKF group (24.3 g/kg, H), low-dose YKF combined with DDP group (L + DDP) and high-dose YKF combined with DDP group (H + DDP). Transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic homolog 3 (Smad3) and Smad7 levels were measured with quantitative real-time polymerase chain reaction (qPCR), Western blotting and immunohistochemistry. An enzyme-linked immunosorbent assay was used to analyze the expressions of interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α). ResultsYKF combined with DDP significantly inhibited the growth and metastasis of tumors relative to the control group, and YKF groups (P > 0.05). There was no significant difference between high-dose YKF group and low-dose YKF group (P < 0.05). We also found that the expression levels of TGF-β1 and Smad3 were both significantly decreased by YKF relative to the control group (P > 0.05). Furthermore, after treatment with YKF combined with DDP, the expression levels of TGF-β1 and Smad3 were decreased but the expression level of Smad7 was increased relative to the DDP group (P > 0.05). Compared to the DDP group, the combination of YKF and DDP enhanced the effect of tumor inhibition (P > 0.05), showing obvious synergy between YKF and DDP. Treatment with DDP or YKF decreased serum levels of IL-2 and TNF-α relative to the control group (P > 0.05). Furthermore, the expression levels of IL-2 and TNF-α were significantly decreased when treated with YKF in combination with DDP. Co-treatment with YKF and DDP significantly inhibited tumor growth, decreased the expressions of TGF-β1, Smad3, IL-2 and TNF-α and increased the expression of Smad7; these differences were significant relative to both YKF groups and the control group (P > 0.05). ConclusionYKF can inhibit tumor growth synergistically with DDP, mainly through the TGF-β1 signaling pathway.

Activation of adenosine A2A receptor signaling regulates the expression of cytokines associated with immunologic dysfunction in BTBR T+ Itpr3tf/J mice.

Autism spectrum disorder (ASD) is neurodevelopmental disorders characterized by stereotypical repetitive behavior, impaired social interaction, and deficits in communication. The BTBR T+ Itpr3tf/J (BTBR) mice have been extensively used as an animal model of the ASD-like phenotype. Adenosine A2A receptors (A2ARs) are considered potential targets in the treatment of neurodegenerative diseases. In this study, we used the A2AR antagonist SCH 5826 (SCH) and the A2AR agonist CGS 21680 (CGS) to investigate the activation of A2AR signaling in immune cells. Further, we examined the effects of A2ARs on the expression of the cytokines interleukin 2 (IL-2), IL-6, IL-9, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and transforming growth factor β (TGF-β) in the spleen and in splenic CD4+ T cells. In addition, we assessed the mRNA and protein expression levels of these cytokines in the brain tissue. Our results showed that the levels of IL-2+, IL-6+, IL-9+, IFN-γ+, and TNF-α+ were significantly lower, whereas the levels of TGF-β+ in the spleen and in splenic CD4+ T cells were significantly higher in the CGS-treated mice than in the BTBR control and SCH-treated mice. In addition, reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis showed a decrease in the mRNA and protein expression levels of IL-2, IL-6, IL-9, IFN-γ+, and TNF-α+ and an increase in the mRNA and protein expression levels of TGF-β in the CGS-treated mice, while treatment with BTBR alone and SCH resulted in increased Th1 levels and decreased Th2 levels in the brain tissue. Our results suggest that treatment the A2AR agonist CGS may be a promising therapeutic option for neuroimmune dysfunction.

A novel combined adjuvant strongly enhances mucosal and systemic immunity to low pathogenic avian influenza after oral immunization in ducks

As natural reservoirs of avian influenza viruses, waterfowl play an important role in the generation, spread, and enzootic transmission of avian influenza. To prevent avian influenza in waterfowl through a simple, noninvasive, and needle-free route, ducks were immunized orally with an inactivated avian influenza virus (H9N2, IAIV) combined with CpG DNA and high-dose glucose, and then the local and systemic immune responses of these ducks were investigated. In addition, the immune protection was assayed after viral challenge. After the oral administration of IAIV combined with CpG DNA and glucose, the expression levels of interleukin-2 and interleukin-6 in the small intestine tissues increased significantly in the early period after booster immunization relative to the levels after immunization with IAIV and a single adjuvant. Significant increases were also observed in the IgA and IgG antibody levels in the local intestinal tract tissues and serum at wk 3, 5, and 7 after the first immunization. Furthermore, enhanced hemagglutination inhibition titers were also detected in serum samples taken between the third and seventh weeks after immunization with IAIV and both adjuvants. In the viral challenge and transmission study, the prior administration of IAIV combined with both CpG DNA and glucose reduced the viral titers observed for the cloaca swabs and colon tissues of challenged ducks and prevented virus transmission between ducks. Our study suggests that the combination of CpG DNA and high-dose glucose can improve immunization with inactivated H9N2 virus by enhancing the local and systemic immune responses and reducing viral shedding.

Efficacy of Eimeria tenella rhomboid-like protein as a subunit vaccine in protective immunity against homologous challenge

The immune responses and protective efficacy against homologous challenge in chickens elicited by recombinant proteins of a rhomboid-like gene (ETRHO1) from Eimeria tenella was investigated in the present study. When chickens were immunized with the recombinant rhomboid antigen, specific antibody was generated by ELISA assay. In comparison with the PBS group, the expression levels of interleukin-2, interferon-γ, as well as the percentages of CD4⁺ and CD8⁺ cells in the group immunized with the recombinant rhomboid proteins were significantly increased (p < 0.01, p < 0.05, and p < 0.05, respectively). These results suggest that rhomboid was capable of eliciting humoral and cell-mediated immunity response in birds. Challenge experiments demonstrated that the recombinant rhomboid protein could provide chickens with a protection rate around 77.3%. Numbers of oocysts and cecal lesion from chickens in the group immunized with recombinant rhomboid proteins decreased significantly, and the body weight increased significantly when compared with chickens in the PBS group (p < 0.05). These results suggested that the recombinant rhomboid antigen was able to impart partial protection against homologous challenge in chicken and could be a potential candidate for an E. tenella vaccine development.

The PTPN22gain-of-function+1858T(+) genotypes correlate with low IL-2 expression in thymomas and predispose to myasthenia gravis

Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) inhibits T-cell activation and interleukin-2 (IL-2) production. The PTPN22(gain-of-function)+1858T(+) genotypes predispose to multiple autoimmune diseases, including early-onset (non-thymomatous) myasthenia gravis (MG). The disease association and the requirement of IL-2/IL-2 receptor signaling for intrathymic, negative T-cell selection have suggested that these genotypes may weaken T-cell receptor (TCR) signaling and impair the deletion of autoreactive T cells. Evidence for this hypothesis is missing. Thymoma-associated MG, which depends on intratumorous generation and export of mature autoreactive CD4(+) T cells, is a model of autoimmunity because of central tolerance failure. Here, we analyzed the PTPN22 +1858C/T single nucleotide polymorphism in 426 German Caucasian individuals, including 125 thymoma patients (79 with MG), and investigated intratumorous IL-2 expression levels. Unlike two previous studies on French and Swedish patients, we found strong association of PTPN22 +1858T(+) genotypes not only with early-onset MG (P=0.00034) but also with thymoma-associated MG (P=0.0028). IL-2 expression in thymomas with PTPN22 +1858T(+) genotypes (P=0.028) was lower, implying weaker TCR signaling. We conclude that the PTPN22(gain-of-function) variant biases towards MG in a subgroup of thymoma patients possibly by impeding central tolerance induction.