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Objective To study the phenotype and function of CD4 +CD25 + Treg cells in the peripheral blood of patients with systemic sclerosis (SSc) and their relationship with fibrosis.Methods The proportion of Foxp3, CD127, CTLA-4 and CD69 on CD4+CD25+ Treg cells in peripheral blood were detect by flow cytometry;the levels of TGF-[1 and IL-10 in serum were detect by enzyme-linked immunosorbent assay (ELISA) in patients with SSc.The correlation between Treg cells and the score of chest HRCT, MRSS, and disease activity was analyzed.T test and Pearson correlation analysis were used for statistical analysis.Results ① Compare to the control group, the proportion of CD4+CD25+ Treg cells in peripheral blood of SSc patients was increased significantly(12.9±2.4 vs 14.9±2.2, t=2.63, P=-0.012), and the expression of CD69+, CTLA-4+ on CD4+CD25+ Treg cells was decreased significantly (P＜0.01).② Compare to the control group, the proportion of CD4+CD25+Foxp3 + cells and CD4+CD25+CDI27-cells in peripheral blood of SSc patients was increased significantly (respectively, 3.3±0.7 vs 5.0±0.7, 5.1±1.6 vs 7.6±2.0, t=7.03, 4.195;P＜0.01), but no correlation between them was detected.③ The level of TGF-β1 in the serum of the SSc patients was lower than that of the control group(86±29 vs 133±29 ng/ml, t=-5.026, P=0.000).However, IL-10 had no significant difference between the two groups.④ The proportion of CD4+CD25 +Foxp3 + cells and CD4~D25 +CD127-cells in peripheral blood of SSc patients was positively correlated with the scores of chest HRCT (respectively, r=-0.541, P=0.02;r=0.486, P=0.041), and no correlation was observed with ESR, CRP.In addition, CD4+CD25+Foxp3+ cells were associated with MRSS.Conclusion The proportion of CD4+CD25+ Treg cells in the peripheral blood of SSc patients is increased, but they alters the immune function.The different phenotypes of Treg cells of CD4+CD25+Foxp3+ cells and CD4+CD25+CD127-cells in peripheral blood of SSc patients are increased significantly, which changes along with skin and lung fibrosis.The associated cytokine TGF-β1 is reduced, and IL-10 is not significantly changed.
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The airway remodeling of bronchial asthma is the result of repeated airway inlfammation. Its occurrence is a complex process involving many cytokines, inlfammatory mediators and associated cellular components, of which leukotrienes are important mediators of inlfammation in the airway remodeling. Many factors inlfuence Airway remodeling. In recent years, effects of Th17 cells and CD4+CD25+regulatory T cells (CD4+CD25+treg cells) on airway remodeling is growing in importance. Leukotriene receptor antagonist is an effective drug in the treatment of asthma and can suppress airway remodeling. But the exact mechanisms and its impact on the proportion of Th17 cells/CD4+CD25+treg cells is not yet clear. Therefore, the clariifcation of the changes of Th17 cells/CD4+CD25+treg cells expression in airway remodeling and the speciifc pathways, biological effects, inlfuence of the proportion of Th17 cells/CD4+CD25+treg cells expression after leukotriene receptor antagonist intervene can provide a new target for prevention and the treatment of asthma in the future.
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Objective To investigate the influence of pinealectomy(Px)and melatonin (MLT) supplementation on CD4~+CD25~+Treg cells development and Foxp3 expression in rat thymus. Methods One hundred and twenty clean-grade male SD rats were divided into five groups: normal control group, sham pinealectomized group, pinealectomized group, Px +7.5 mg/(kg·d) MLT group, Px +15 mg/(kg·d) MLT group, and the thymus were taken out at the 4th week and the 8th week;Flow cytometric analysis was used to analyse the number of double positive cells in the thymus and peripheral blood;Semiquantitative RT-PCR and immunohistochemistry were applied to analyse Foxp3 expression of rat thymus. Results There was no difference of the number of CD4~+CD25~+ Treg cells in rat thymus between Px and normal/sham group, and the number increased dependently on time and dose after MLT supplementation. In rat peripheral blood the double positive cells significantly increased in models of Px at the 4th week, and then backed to normal level after MLT supplementation. The results showed no significant changes in all groups at the 8th weeek;At the 4th weeks, Foxp3 expression increased in the thymus of Px rats compared to nomal/sham group, which returned to normal level after MLT supplementation. On the other hand, Foxp3 expression showed no significant difference in all groups at the 8th weeek.Conclusion Px made no difference between the development of CD4~+CD25~+Treg cells in rat thymus, but resulted in significant increase of thymic output and Foxp3 expression. All the effects disappeared at the 8th week. MLT supplementation could reverse the abnormity.
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Objective:To explore the influence of tumor cells on CD4~+ CD25~+ Treg cells via TLRs.Methods:The numbers changes of CD4~+ CD25~+ Treg cells in the co-culture system of Lewis lung cancer cells and splenic lymphocytes were detected by flow cytometry;The expression of Foxp3 and TLR1-9 mRNA after co-culture were detected by RT-PCR;TLR9 expression on Lewis lung cancer cells was blocked by TLR9 receptor antagonist chloroquine.Results:Compared with control group,the number of CD4~+ CD25~+ Treg cells and Foxp3 mRNA expression were significantly increased in the co-culture group (P＜0.05).The expression of a variety of TLRs were affected by the co-culture of lymphocytes with Lewis lung cancer cells,and TLR9 mRNA expression was significantly increased compared with that of the control group (P＜0.05);Blocking TLR9 of Lewis lung cancer cells significantly reduce CD4~+ CD25~+ Treg cells and Foxp3 mRNA (P＜0.05).Conclusion:Lewis lung cancer cells could increase both number and function of CD4~+ CD25~+ Treg cells through inducing TLR9 expression in immunocells.This might be one of mechanisms of tumor-induced immune tolerance,and by which to contribute to the occurrence and progression of tumors.
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Objective:To explore the influence of tumor cells on CD4+CD25+Treg cells via TLRs.Methods:The numbers changes of CD4+CD25+Treg cells in the co-culture system of Lewis lung cancer cells and splenic lymphocytes were detected by flow cytometry;The expression of Foxp3 and TLR1-9 mRNA after co-culture were detected by RT-PCR;TLR9 expression on Lewis lung cancer cells was blocked by TLR9 receptor antagonist chloroquine.Results:Compared with control group,the number of CD4+CD25+Treg cells and Foxp3 mRNA expression were significantly increased in the co-culture group(P
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Objective:To investigate the Foxp3 expression in murine model of type 1 diabetes mellitus and the effects of Foxp3 in the pathogenic mechanism of type 1 diabetes mellitus.Methods:Type 1 diabetes mellitus of mouse was induced by STZ.The Foxp3 expression in the spleen cells was detected at the mRNA level by RT-PCR and at protein level by Western blot.The percentage of CD4+CD25+ Treg cells in the spleens were detected by Flow cytometry.Results:The expressing levels of Foxp3 mRNA and scurfin in the model group was higher than those of control group within the first week after induction,but the expressing level of Foxp3 mRNA and Scurfin began to decrease on day 7 and were lower than those of control group on day 30.The percentage of CD4+CD25+ Treg cells in model group was similar with that of control group within the first week after induction,but after day 7,the percentage of CD4+CD25+ Treg cells in model group began to get lower than contol group.Conclusion:The expressing level of Foxp3 is decreased,then the proportion of CD4+CD25+ Treg cells is decreased accordingly,which may contribute to the pathogenic mechanism in type 1 diabetes mellitus.