m 6A RNA Methylation Decreases Atherosclerotic Vulnerable Plaque Through Inducing T Cells

ABSTRACT Introduction: Knockdown of fat mass and obesity-associated gene (FTO) can induce N6-methyladenosine (m 6A) ribonucleic acid (RNA) methylation. The objective of this study was to explore the effect of m 6A RNA methylation on atherosclerotic vulnerable plaque by FTO knockdown. Methods: A total of 50 New Zealand white rabbits were randomly divided into pure high-fat group, sham operation group, vulnerable plaque group, empty load group, and FTO knockdown group (10 rabbits/group). Results: Flow cytometry showed that helper T (Th) cells in the FTO knockdown group accounted for a significantly higher proportion of lymphocytes than in the vulnerable plaque group and empty load group (P<0.05). Th cells were screened by cell flow. The level of m 6A RNA methylation in the FTO knockdown group was significantly higher than in the vulnerable plaque group and empty load group (P<0.05). The levels of total cholesterol, triglyceride, and low-density lipoprotein C were higher at the 12th week than at the 1st week, but the high-density lipoprotein C level was lower at the 12th week than at the 1st week. At the 12th week, the interleukin-7 level was significantly lower in the adeno-associated virus-9 (AVV9)-FTO short hairpin RNA group than in the control and AVV9-green fluorescent protein groups (P<0.001). Conclusion: After successfully establishing a vascular parkinsonism rabbit model, m 6A RNA methylation can decrease Th cells and vulnerable atherosclerotic plaques.

Diagnostic value of soluble interleukin 7 receptor in combination with other biomarkers for emergency sepsis / 中国医师杂志

Objective:To investigate the diagnostic value of soluble interleukin 7 receptors (sIL-7R) in combination with other biomarkers for emergency sepsis.Methods:A prospective study method was used to select 102 emergency patients from the Chuiyangliu Hospital affiliated to Tsinghua University and Baoding First Central Hospital from December 2020 to June 2022. They were divided into sepsis group (80 cases) and non-sepsis group (22 cases), and 20 healthy people in the same period were selected as the control group. The patient data were collected, the relevant biomarker examination was improved and the values were recorded. Using statistical methods, the significance of sIL-7R for the diagnosis of sepsis was assessed, and important indicators related to the presence of sepsis were also screened to construct a model for the early diagnosis of sepsis.Results:The levels of interleukin-6 (IL-6), C-reactive protein (CRP), age and sIL-7R in sepsis group were significantly higher than those in non-sepsis group and control group (all P<0.01). Further, the sIL-7R, age, CRP, and IL-6 were selected as important diagnostic indicators of sepsis by comparing the sepsis and non-sepsis groups using R-language statistical software. Receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC) for diagnosing sepsis of the four indexes were calculated as 0.759, 0.622, 0.716 and 0.640, respectively. The diagnostic model based on the four indexes performed better than other indexes, and the AUC value reached 0.869. The AUC of sIL-7R in the diagnosis of sepsis was higher than that of the other three indexes, and the detection of SIL-7R in combination with other inflammatory indexes was significantly higher than that of the four indexes, which had obvious advantages for the early diagnosis of sepsis. Conclusions:sIL-7R is a good biological marker for the early diagnosis of sepsis, and its combination with age, CRP, and IL-6 can better improve the early diagnosis of sepsis.

Expression Level and Significance of Tim-3 in CD4+ T Lymphocytes in Peripheral Blood of Patients with Coronary Heart Disease

Abstract Objective: To investigate the expression level and significance of T cell immunoglobulin and mucin-domain containing molecules-3 (Tim-3) and interleukin-7 (IL-7) in CD4+ T lymphocytes in peripheral blood of patients with coronary heart disease (CHD). Methods: 75 patients with CHD treated at our hospital were selected and classified as mild group (25 cases), moderate group (25 cases) and severe group (25 cases), according to the severity of illness. Twenty-five healthy volunteers who underwent a physical examination at our hospital during the same period were selected as the control group. The expression level of Tim-3 in CD4+ T lymphocytes in peripheral blood of patients in four groups was detected by flow cytometry and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The expression level of IL-7 in peripheral blood serum was measured by enzyme-linked immunosorbent assay (ELISA). Correlation analyses of Tim-3 and IL-7, Tim-3 and disease severity and IL-7 and disease severity were performed, respectively. Results: Flow cytometry and qRT-PCR demonstrated that the expression of Tim-3 in CD4+ T lymphocytes in peripheral blood of patients with CHD increased with the aggravation of the disease. ELISA showed that the tendency of IL-7 expression in peripheral blood serum was consistent with the expression of Tim-3, and the expression of Tim-3 had a positive correlation with IL-7. The expression levels of both Tim-3 and IL-7 were positively correlated with the Gensini score. Conclusion: The expression of Tim-3 and IL-7 in peripheral blood of patients with CHD was upregulated and increased with the aggravation of CHD.

Immunomodulatory mechanism of interleukin-7 receptor α antibody attenuating renal injury in MRL/lpr lupus mice / 中华肾脏病杂志

Objective:To investigate the effect of interleukin (IL)-7 receptor α (IL-7Rα) antibody on the immune inflammation and renal injury in MRL/lpr lupus mice.Methods:Fifteen 3-4-week-old female MRL/lpr lupus mice (specific pathogen free) weighing 15-16 g were bred to 14-week-old and randomly divided into three groups: IL-7Rα antibody intervention group, isotype antibody (positive control) group and normal saline (negative control) group. The mice in the threc groups were intraperitoneally injected with IL-7Rα antibody, isotype antibody and normal saline respectively, with 100 μg three times a week for 4 weeks. At the age of 18-week old, the mice were sacrificed. Twenty-four-hour urinary protein was detected by Coomassie brilliant blue method, serum creatinine was detected by peroxidase method, and the expression of autoantibody (anti-double strand DNA antibody) and inflammatory factors such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-21 was detected by enzyme-linked immunosorbent assay method. Renal pathology was detected by PAS and Sirius red staining, and CD3 and F4/80 in renal tissues were detected by immunohistochemistry method. Regulatory T cells, follicullar helper T cells (Tfh) and follicular regulatory T cells (Tfr) were detected by flow cytometry.Results:The 24-hour urinary protein, serum creatinine, serum anti-double strand DNA antibody and serum IFN-γ and IL-21 in the IL-7Rα antibody intervention group were significantly lower than those in the control groups (all P<0.01). However, there was no significant difference in serum TNF-α among the three groups ( F=0.39, P>0.05). The positive infiltrating cells of CD3 and F4/F80, and the ratio of type Ⅰ/Ⅲ collagen fibers ( F=41.11, P<0.01) of renal tissues in the IL-7Rα antibody intervention group were lower than those in the other two groups. Compared with the control groups, the ratio of regulatory T cells (CD4 +CD25 +Foxp3 +)/effector T cells (CD4 +CD25 +) in blood of IL-7Rα antibody intervention group increased ( F=21.64, P<0.01), while the ratio of Tfr (CD4 +CXCR5 +Foxp3 +)/Tfh (CD4 +CXCR5 +) in peripheral blood and spleen increased ( F=38.95, P<0.01; F=12.90, P<0.01). Conclusion:IL-7Rα antibody can reduce the production of autoantibodies such as anti-double strand DNA antibody and inflammatory factors by increasing the ratio of regulatory T cells and Tfr/Tfh, thus alleviating immune inflammation and renal damage in MRL/lpr lupus mice.

The regulation of interleukin-7/CD 127 signaling pathway on CD 8+T cells in patients with myasthenia gravis / 中华神经科杂志

Objective:To investigate the modulatory function of interleukin-7 (IL-7)/CD 127 signaling pathway on CD 8+T cells in patients with myasthenia gravis (MG). Methods:Fifty-seven treatment-naive MG patients who were hospitalized in Department of Neurology, Nanyang Central Hospital between 2017 and 2020 as well as 35 healthy controls were enrolled. Peripheral blood was collected, while plasma and peripheral blood mononuclear cells were isolated. Plasma IL-7 and soluble CD 127 (sCD 127) were measured by enzyme linked immunosorbent assay (ELISA). Membrane-bound CD 127 (mCD 127) percentage in CD 8+T cells was measured by flow cytometry. The differences of above indices between different gender, onset age, afflicting with thymoma, or different Osserman type and their correlation with Quantitative Myasthenia Gravis (QMG) score were analyzed. Purified CD 8+T cells from MG patients were stimulated with recombinant human IL-7 (5 μg/L). Changes of sCD 127 and mCD 127 level were analyzed. Levels of perforin, granzyme B, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) in the cultured supernatants were measured by ELISA. Immune checkpoint molecules mRNA in CD 8+T cells was semi-quantified by real-time fluorescence quantitative polymerase chain reaction. Results:Plasma IL-7 level was up-regulated in MG patients compared with controls [(293.4±74.7) pg/ml vs (233.8±70.8) pg/ml, t=3.78, P<0.001], while sCD 127 level was down-regulated in MG patients compared with controls [(102.7±13.7) pg/ml vs (131.2±20.9) pg/ml, t=7.91, P<0.001]. Peripheral CD 8+T cells percentage was up-regulated in MG patients compared with controls (35.4%±7.1% vs 30.2%±7.5%, t=3.31, P=0.001), and mCD 127+CD 8+T cell percentage was also elevated (45.5%±7.7% vs 34.7%±11.5%, t=5.44, P<0.001). There were no significant differences of above indices between different gender, onset age, afflicting with thymoma, or different Osserman type. There was no significant correlation between above indices and QMG score. There were no significant differences of sCD 127 in cultured supernatants, mCD 127+CD 8+T cell percentage, or immune checkpoint molecules mRNA expression between CD 8+T cells from MG patients with and without IL-7 stimulation. IL-7 stimulation promoted the secretion of perforin [(208.1±67.2) pg/ml vs (168.8±46.2) pg/ml, t=2.16, P=0.038], granzyme B [(941.8±273.9) pg/ml vs (782.4±137.2) pg/ml, t=2.33, P=0.025], and IFN-γ [(19.1±5.2) pg/ml vs (15.3±4.5) pg/ml, t=2.47, P=0.018] by CD 8+T cells. However, there was no remarkable difference of TNF-α production between CD 8+T cells with and without IL-7 stimulation. Conclusion:Elevated IL-7-mediated signaling pathway enhanced the secretion of cytotoxic molecules and cytokines by CD 8+T cells, leading to increased activity of CD 8+T cells in MG patients.

Action mechanisms of thymic stromal lymphopoietin in various skin diseases / 中华皮肤科杂志

Thymic stromal lymphopoietin (TSLP) , a cytokine similar to interleukin-7 (IL-7) , can promote the differentiation and proliferation of a variety of cells, promote the secretion of Th2 cytokines by these cells, and plays an important role in the immune system. In recent years, abnormal expression of TSLP has been found in many skin diseases, and its level is also related to the severity of some skin diseases, suggesting that TSLP may be a potential target for the treatment of various skin diseases. This review summarizes recent research progress in the role of TSLP in the occurrence and development of various skin diseases, including inflammatory diseases, immune diseases, genetic diseases and tumors, and provides a basis and some ideas for the diagnosis and treatment of related diseases.

Clinical significance of ascitic interleukin-7 expression levels in cirrhotic patients complicated with spontaneous bacterial peritonitis / 中华肝脏病杂志

Objective@#To observe ascitic interleukin-7 expression level in cirrhotic patients complicated with spontaneous bacterial peritonitis, and to detect the effect of recombinant human IL-7 on CD4+ and CD8+T lymphocyte function.@*Methods@#A total of 84 patients with liver cirrhosis who were hospitalized from August 2017 to April 2018 were selected. Among them, 51 cases were complicated with cirrhosis and untainted ascites, and 33 cases were cirrhosis complicated with spontaneous bacterial peritonitis. Peripheral blood and ascites were collected routinely. The levels of IL-7 in peripheral blood and ascites were measured by enzyme-linked immunosorbent assay. CD4+T cells and CD8+T cells were purified from ascites, and were stimulated with recombinant IL-7. Cellular proliferation, key transcription factors for mRNA, and cytokines production by CD4+T cells in response to IL-7 stimulation was measured. mRNA expression corresponding to perforin, granzyme B, and granulysin as well as cytokines production by CD8+T cells was also measured in response to IL-7 stimulation. Cytolytic and non-cytolytic activity of CD8+T cells in response to IL-7 stimulation was also investigated in both direct and indirect contact co-culture system. Measurement data of the normal distribution were compared between the two groups by Student’s t-test and the data before and after stimulation were compared by paired t-test. Measurements that did not conform to normal distribution were compared between the two groups using Mann-Whitney U test, and data before and after stimulation were compared using Wilcoxon paired test.@*Results@#There was no significant statistical difference in serum IL-7 levels between the two groups [(5 001 ± 1 458) pg/ml vs. (4 768 ± 1 128) pg/ml, P = 0.41]. The level of ascitic IL-7 in cirrhotic patients complicated with SBP was significantly lower than cirrhosis patients with untainted ascites [(966.4 + 155.8) pg/ml vs. (792.1 + 126.4) pg/ml, P < 0.01]. Recombinant IL-7 stimulation promoted the proliferation of CD4+ and CD8+T cells from ascites in patients with liver cirrhosis complicated by SBP. T-bet mRNA relative expression and IFN-γ secretion in CD4+T cells was also elevated in response to IL-7 stimulation in vitro. Moreover, IL-7 stimulation also increased the mRNA expressions of perforin, granzyme B, and granulysin as well as productions of IFN-γ and TNF-α by CD8+T cells. Recombinant IL-7 stimulation elevated cytolytic and non-cytolytic activity of CD8+T cells from ascites in patients with liver cirrohosis complicated by SBP, which manifested as increased target cell death and IFN-γ production in both direct and indirect contact co-culture system.@*Conclusion@#Ascitic IL-7 promotes T lymphocyte function in patients with liver cirrhosis complicated with SBP.

Effect of the anti-IL-17 antibody on allergic inflammation in an obesity-related asthma model

BACKGROUND/AIMS: The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. METHODS: High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. RESULTS: HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. CONCLUSIONS: These results suggest that the IL-17–leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

Changes of levels of IL-7 and IL-10 in peripheral blood of patients with different clinical stages of eczema and their clinical significances / 吉林大学学报(医学版)

Objective: To detect the levels of interleukin-7 (IL-7) and IL-10 in peripheral blood of the patients with different clinical stages of eczama, and to elucidate their clinical significances. Methods: Ninety patients with eczema were selected, and divided into acute eczama group (n=30), subacute ecxama group (n=30), and chronic eczama group (n=30). Meanwhile, 30 healthy people who went to hospital for physical examination during the same period were recruited as control group. The relative expression levels of cytokines IL-7 and IL-10 mRNA in peripheral blood of the subjects in various groups were detected by RT-PCR method. The levels of IL-7 and IL-10 in peripheral blood of the subjects in various groups were measured by ELISA method. The eczema area and severity index (EASI) scores of the subjects in various groups were detected. The relationships between IL-7 level, IL-10 level and EASI scores were analyzed. Results: Compared with control group, the relative expression levels IL-7 and IL-10 mRNA in peripheral blood of the patients with different clinical stages of eczenma were significantly increased (F= 3. 17, P= 0. 04; F= 4. 73, P = 0. 02); the expression levels of IL-7 and IL-10 in peripheral blood of the patients with different clinical stages of eczema were significantly increased (F= 6. 23, P<0. 01; F= 5. 34, P= 0. 01). The levels of IL-7 and IL-10 were positively correlated with the corresponding mRNA relative expression levels in peripheral blood of the patients with different clinical stages of eczema (r= 0. 95, P<0. 01; r= 0. 94, P<0. 01) and EASI scores of the patients (r=0. 88, P<0. 01; r= 0. 89, P<0. 01), which were increased along with the increasing of severity degree of the patients. Conclusion: The levels of IL-7 and IL-10 of the patients with eczema are significantly higher than those in the healthy controls, which are positively correlated with the severity of the disease. The cytokines IL-7 and IL-10 may be involved in the pathological process of eczema, and the detection of their experssion levels contributes to assess the severity of disease.

Relationship between interleukin-7 and the adaptive immune disorders in sepsis / 中国小儿急救医学

Sepsis remains the leading cause of death of patients in pediatric intensive care unit. The adaptive immune dysfunction affects the occurrence and development of sepsis. Recent studies have found that interleukin-7 plays a critical part in the immune cell activation,proliferation and maturation,and it may have important means in the immune reconstitution in sepsis. Immunosuppression,the biological function of inter-leukin-7,the immune cell regulation and its application progress in sepsis were reviewed in this article.

Osteoblast-derived IL-7 Prohibits Bone Formation through Activating mTORC1 Signaling / 医学研究杂志

Objective To investigate the regulation of bone formation by osteoblast-derived interleukin-7 (IL-7) trough the mammalian target of rapamycin (mTOR) signaling pathway.Methods The lentiviral vector with encoding frame of IL-7 gene was transfected into mouse MC3T3-E1 osteoblasts,and the expression levels of IL-7 mRNA and protein were detected,respectively,by qRT-PCR and ELISA method.Western blot method was used to detect the expression levels of P-S6,S6,collagen Ⅰ (Col Ⅰ) and Osteocalcin (Ocn) in MC3T3-E1 cells and in MC3T3-E1 cells stimulated by 0.1nmol/L mTORC1-specific inhibitor rapamycin.Results The IL-7 mRNA level of MC3T3-E1 cells transfected with upregulated 4.6 times,and ELISA assay showed an increase of 3.9 times of IL-7 level in osteoblastic supernatants.After transfected using lentiviral vector with encoding frame of IL-7 gene,the expression levels of P-S6 protein increased significantly,while the expression levels of Col Ⅰ and Ocn protein decreased significantly.However,rapamycin treatment of over-expressed-IL-7 MC3T3-E1 cells resulted in a decline of P-S6 protein levels,but an increase of Col Ⅰ and Ocn protein levels.Conclusion Osteoblast-derived IL-7 may inhibit its maturation by promoting mTORC1 signaling pathway.

Plasmacytoid Dendritic Cells Contribute to the Protective Immunity Induced by Intranasal Treatment with Fc-fused Interleukin-7 against Lethal Influenza Virus Infection

Developing a novel vaccine that can be applied against multiple strains of influenza virus is of utmost importance to human health. Previously, we demonstrated that the intranasal introduction of Fc-fused IL-7 (IL-7-mFc), a long-acting cytokine fusion protein, confers long-lasting prophylaxis against multiple strains of influenza A virus (IAV) by inducing the development of lung-resident memory-like T cells, called T(RM)-like cells. Here, we further investigated the mechanisms of IL-7-mFc-mediated protective immunity to IAVs. First, we found that IL-7-mFc treatment augments the accumulation of pulmonary T cells in 2 ways: recruiting blood circulating T cells into the lung and expanding T cells at the lung parenchyma. Second, the blockade of T cell migration from the lymph nodes (LNs) with FTY720 treatment was not required for mounting the protective immunity to IAV with IL-7-mFc, suggesting a more important role of IL-7 in T cells in the lungs. Third, IL-7-mFc treatment also recruited various innate immune cells into the lungs. Among these cells, plasmacytoid dendritic cells (pDCs) play an important role in IL-7-mFc-mediated protective immunity through reducing the immunopathology and increasing IAV-specific cytotoxic T lymphocyte (CTL) responses. In summary, our results show that intranasal treatment with IL-7-mFc modulates pulmonary immune responses to IAV, affecting both innate and adaptive immune cells.

Effect of remifentanil on metastasis of human lung adenocarcinoma cells and expression of interleukin-7 receptors / 中华麻醉学杂志

Objective To evaluate the effects of remifentanil on the metastasis of human lung adenocarcinoma cells and expression of interleukin-7 receptor (IL-7R).Methods Human adenocarcinoma cell line A549 cells were seeded in 24-well plates at a density of 2× 105 cells/ml (72 wells).The cells were divided into 4 groups (n =18 each) using a random number table:normal control group (group C) and remifentanil 2,4 and 6 ng/ml groups (group R2,group R4,group R6).In R2,R4 and R6 groups,remifentanil at the final concentrations of 2,4 and 6 ng/ml was added,respectively,and the cells were incubated for 4 h.The equal volume of normal saline was given instead of remifentanil in group C.The cells were collected at 24 h after the following incubation.The invasion of cells was determined by Transwell invasion assay,and the invaded cells were counted.The migration of cells was determined by cell scratch test,and cell migration rates were calculated.The expression of IL-7R in cells was detected by Western blot.Results Compared with group C,the number of invaded cells and cell migration rates were significantly decreased in R2,R4 and R6 groups,and the expression of IL-7R was down-regulated in R4 and R6 groups (P＜0.05).Compared with group R2,the number of invaded cells and cell migration rates were significantly decreased,and the expression of IL-7R was down-regulated in R4 and R6 groups (P＜0.05).Compared with group R4,the number of invaded cells and cell migration rates were significantly decreased,and the expression of IL-7R was down-regulated in group R6 (P＜0.05).Conclusion Remifentanil can inhibit metastasis of human lung adenocarcinoma cells and down-regulate the expression of IL-7R.

The research progress of interleukin 7 receptor in the development of lymphocytes and pathogenesis of multiple sclerosis / 天津医药

Interleukin 7 receptor (IL7R) is a transmembrane receptor that belongs to the typeⅠcytokine receptor fami-ly. It consists of the cytokine-specific α-chain (IL7Rα, CD127) and the shared common cytokine γ-chain (γc, CD132). IL-7R is expressed in various cell types, including lymphoid precursor cells, pro-B cells, T cells, thymocytes, dendritic cells, myeloid cells and monocytes. Under physiological conditions, IL7R is a vital cytokine for development and survival of T and B cells. IL7R plays a key role in the pathogenesis of multiple sclerosis (MS). Single nucleotide polymorphisms (SNPs) in the gene encoding IL7Rαhave emerged through genetic studies of MS patients. In experimental autoimmune encephalomy-elitis (EAE) mouse model of MS, treatment with neutralizing anti-IL7Rαantibody results in significant improvement of EAE. Therefore, IL7R may serve as a novel target for MS therapies.

The level of souble interleukin 7receptor in serum from lupus nephritis patients and clinical implication / 实用医学杂志

Objective To investigate the level of soluble interleukin 7 receptor (sIL-7R) in serum of lupus nephritis(LN)patients and evaluate its clinical significance. Methods sIL-7R level in serum of LN patients and healthy controls were measured by ELISA , while total 24 hours urinary protein and complement C3 of LN patients were measured by BN ProSpec. The level of sIL-7R correlation with SLEDAI, total 24 hours urinary protein and complement C3 were analyzed respectively. Results The levelof sIL-7R was higher in serum of LN patients than healthy controls (P < 0.01). Moreover, its expression in serum was increased in LN patients in active stage than in LN patients in stable stage (P < 0.05). The level of sIL-7R was positively assosicated with SLEDAI, total 24 hours urinary protein(P < 0.01, P < 0.05) and negatively with complement C3 (P < 0.05). Conclusion The level of sIL-7R is upregulated in serum in LN patients and correlated with disease activity and progression, so it may be expected to become a potential marker of disease in prediction.

Study of the association between difference in cellular immunity and liver function of hepatitis B virus genotype B,C and interleukin-7 inducing follicular helper T lymphocytes / 中华传染病杂志

Objective To investigate the association between the difference of specific cytotoxic lymphocyte (CTL) and liver function of patients with hepatitis B virus (HBV) genotype B and C infections and interleukin (IL)‐7 induced follicular helper T lymphocytes (Tfh) .Methods Sixty‐seven patients with chronic hepatitis B (CHB) hospitalized at Wuxi No .5 People′s Hospital from August 2013 to January 2015 were collected and 30 healthy blood donors were set as healthy control group .The peripheral blood IL‐7 , Tfh ,IL‐21 ,HBV specific‐CTL ,nonspecific CTL ,levels of HBV DNA ,alanine aminotransferase (ALT) and total bilirubin (TBil) were compared between patients with genotype B and C infection ,hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative CHB ,high ALT level and low ALT level .Multivariate regression analysis was performed to determine the factors associated with IL‐7 .The t test was used for quantitative data and chi‐square test was used for categorical data .Results Of the 67 CHB patients with average age of (35 .1 ± 11 .4) ,48 were male and 19 were female;32 were infected with genotype C and 35 were infected with genotype B ;40 were HBeAg‐positive CHB and 27 were HBeAg‐negative CHB ;17 were with high ALT levels and 50 were with low ALT levels .IL‐7 ,Tfh ,IL‐21 and HBV specific‐CTL levels in the peripheral blood of genotype C‐infected patients were (20 .79 ± 4 .82 ) ng/L , (3 .93 ± 0 .82)% ,(24 .77 ± 7 .52) ng/L and (0 .20 ± 0 .04)% ,respectively ,while in genotype B‐infected patients , those were (29 .13 ± 8 .17) ng/L ,(5 .92 ± 1 .92)% ,(39 .94 ± 24 .00) ng/L and (0 .40 ± 0 .06)% , respectively .Levels of IL‐7 , Tfh ,IL‐21 and HBV specific‐CTL in genotype C‐infected patients were significantly lower than those in genotype B‐infected patients (t= 5 .027 ,5 .595 ,3 .553 and 15 .133 , respectively ;all P<0 .01) .Nonspecific CTL ,HBV DNA ,ALT and TBil levels in the peripheral blood of genotype C‐infected patients were all significantly higher than those in genotype B infected‐patients (t=4 .899 ,6 .815 ,2 .763 and 4 .899 ,respectively ;all P< 0 .01) .IL‐7 ,Tfh ,IL‐21 ,HBV specific‐CTL levels in the peripheral blood of HBeAg‐positive patients were significantly lower than those in HBeAg‐negative patients (all P<0 .01) .Nonspecific CTL ,HBV DNA ,ALT and TBil levels in the peripheral blood of HBeAg‐positive patients were all significantly higher than those in HBeAg‐negative patients (all P<0 .05) .IL‐7 ,Tfh ,IL‐21 ,HBV specific‐CTL levels in the peripheral blood of patients with high ALT levels were all significantly lower than those in patients with low ALT levels (all P<0 .01) .Nonspecific CTL and HBV DNA levels in the peripheral blood of patients with high ALT levels were both significantly higher than those in patients with low ALT levels (both P<0 .01) .HBV DNA ,IL‐21 and nonspecific CTL were all correlated with IL‐7 (all P<0 .01) .Conclusion The differences of HBV specific‐CTL and liver function in CHB patients infected with genotype B and C may be correlated with interleukin‐7 induced Tfhcells.

Serum levels of interleukin-7 and interleukin-8 in head and neck squamous cell carcinoma.

Background: The aim of this study was to investigate the association of head and neck squamous cell carcinoma (HNSCC) with serum levels of interleukin-7 (IL-7) and IL-8, the two cytokines whose associations with HNSCC need more clarifications. Materials and Methods: Commercial enzyme-linked immunosorbent assay kits were used for the quantification of the cytokines. Sera were collected from 48 untreated patients (36 men and 12 women; mean age: 52.7 ± 9.8 years) and 34 healthy donors (26 men and 8 women; mean age: 53.1 ± 9.0 years). Results: Serum IL-8 level was neither significantly different between HNSCC patients and control individuals nor associated with smoking status, gender, age, tumor location, tumor grade, and stage of the patients (P > 0.05). Regarding IL-7, all control individuals had serum levels below the sensitivity of the kit (3 pg/ml), but nine patients had detectable levels, and that the mean serum IL-7 was significantly higher in the patients compared to the controls (P = 0.008). Conclusions: Serum IL-8 level is not significantly associated with HNSCC. With the sensitivity of the kit we employed, it seems that serum IL-7 levels are specifically elevated in HNSCC patients compared to healthy individuals. Data from other independent studies are required to clarify the possible employment of IL-7 as an HNSCC biomarker.

Polymorphisms in Interleukin-2 and Interleukin- 7 Receptor α-Chain Genes and Human Herpes Virus-6 as Risk Factors for Multiple Sclerosis.

Aim: The aim of this study was to examine whether a Human herpes virus-6 (HHV-6) infection increases the risk of MS in individuals harboring particular cytokine receptor α- chain gene alleles. Study Design: MS patients and controls were assessed for HHV-6 DNA and for single nucleotide polymorphisms (SNPs) in their IL7RA and IL2RA genes. Place and Duration of Study: The study was carried out at the Department of Experimental Pathology, Microbiology and Immunology, American University of Beirut, between March 2011 and March 2013. Methodology: Blood samples from 100 MS patients and 100 controls were investigated for the presence of HHV-6 by nested PCR. Single nucleotide polymorphisms (SNPs) in the IL7RA and IL2RA genes were examined by restriction fragment length polymorphism. Results: HHV-6 was detected in 58% of MS patients and 32% of controls (OR = 2.935, 95% CI = 1.582-5.463, p=0.000). We did not detect a statistically significant correlation between MS and the studied rs2104286, rs12722489 SNPs in the IL2RA gene and rs6897932 SNP in the IL7RA gene. Concomitant presence of rs2104286 and HHV-6 was detected in 56% of patients and 30% of controls (OR=2.970, 95% CI=1.594-5.53, P=0.000). Similarly, rs6897932 and HHV-6 were observed in 57% of patients and 28% of controls (OR=3.409, 95% CI= 1.815-6.428, P=0.000). Therefore, double positivity moderately increased the risk of MS compared to either factor alone. HHV-6 and rs12722489 double positivity did not increase the risk of MS. Conclusion: HHV-6 infections may enhance the risk of MS in subjects with particular genetic determinants.

Preliminary study on IL-7 receptor α combined with bacterial flagellin intervening acute graft-versus-host disease of mice after allogeneic bone marrow transplantation / 白血病·淋巴瘤

Objective To compare the effects between the impact of IL-7Rα,bacterial flagellin alone to the acute graft-versus-host disease and the combination of both,and to explore its possible mechanism.Methods The BALB/C (H-2d) female mice as recipients were divided into alone irradiation transplantation group (group A),IL-7Rα intervention group (group B),bacterial flagellin intervention group (group C),IL-7Rα combined with bacterial flagellin intervention group (group D),and 6 mice in each group.All mice were accepted 9 Gy 60Co total body irradiation,and 1×107 bone marrow cells and 2× 107 spleen cells of donors C57BL/6 (H-2b) mice were infused via the tail vein to recipient mice.The symptoms,signs,survival time and hematopoietic function recovery of the recipient mice were observed.Results Mice survival of group A was (22.5±2.30) d,30 d survival rate was 50.0 ％ (3/6),and aGVHD performances inculding the fatigue,anorexia,hair removal,arched,and so on appeared obviously.Survival of group B was (25.83±3.49) d,30 d survival rate was 33.3 ％ (2/6),aGVHD performances compared with group A was lighter.Survival of group C was (26.33±3.52) d,30 d survival rate was 33.3 ％ (2/6),also appeared aGVHD performance,which degree was same to the group B.survival of group D was (30.17±2.86) d,30 d survival rate was 66.7 ％ (4/6),aGVHD performances compared to the other three groups was lightest.The white blood cell count of four groups were reduced to minimum at +7 d,then the three intervention groups gradually recovered.The WBC recovery at 14,21,28,30 day after the transplant of group A compared with slowly was the intervention groups (P ＞ 0.05),WBC recovery of B was roughly equal to group C (P ＞ 0.05),while the WBC recovery of group D was faster than group B or C (P ＜ 0.05).At 2nd week after transplantation,CD3+ T cells was significantly decreased in 4 groups,and at 3rd week began gradually rised.Compared with group A,the proportion of CD3+ cells of other three groups were increased significantly,there was no statistical signifiance of CD3+ cell proportion between group B and group C at 2nd,3rd,4th week after transplantation (P ＞ 0.05),while the CD3+ T cell recovery in group D was faster than group B or C (P ＜ 0.05).Conclusions The stable aGVHD mouse model was established.Exogenous IL-7Rα and bacterial flagellin may reduce the incidence of aGVHD.There was no significant difference for aGVHD when they was used alone,but when combination of them,aGVHD is slighter and the hematopoietic recorery is faster.

The expression level of serum IL-7 and its influence on prognosis in patients with acute coronary syndrome / 心血管康复医学杂志

Objective: To explore the expression level of serum interleukin (IL)-7 in patients with acute coronary syndrome (ACS) and analyze the relationship between IL-7 level and prognosis. Methods: A total of 130 ACS patients [ACS group, including 70 cases with acute myocardial infarction (AMI) and 60 cases with unstable angina pectoris (UAP)], 33 cases with stable angina pectoris (SAP，SAP group) and 89 healthy subjects (healthy control group) were selected. IL-7 level was measured using enzyme linked immunosorbent assay (ELISA) and compared among all groups. The 130 ACS patients were followed up, and Logistic regression analysis was used to analyze the relationship between IL-7 level and prognosis. Results: Compared with healthy control group and SAP group, there was significant rise in IL-7 level in UAP group and AMI group [(1.84±0.47) pg/ml, (2.11±0.63) pg/ml vs. (4.87±0.52) pg/ml, (5.15±0.71) pg/ml, P0.05 both); Logistic regression analysis indicated that expression level of serum IL-7 was an independent risk factor for adverse cardiovascular events in ACS patients (OR=1.212, 95%CI:1.061-1.418). Conclusion: Interleukin-7, as an important inflammatory cytokines, its serum level abnormally elevated in patients with acute coronary syndrome, it may have important prognostic value.