The Effect Of Cyclosporine On Regulatory T Cell And IL-17Gene In The Peripheral Blood Of Children With Chronic Aplastic Anemia

Aplastic Anemia is diagnosed by the low amount of one marrow hematopoietic stem cell caused by physicochemical,biological,pharmaceutical and other unknown factors,bone marrow hematopoietic function failure caused by the damage of hematopoietic microenvironment,and the pancytopenia(which means lower counts of all three blood cell types:red blood cells,white blood cells,and platelets).This disease harms greatly to patients,and it has high mortality,long treatment duration,and low curative effect,which occurs more frequently in Children.Thus,since Aplastic Anemia has been reported,the discussion about its pathogenesis is ceaseless.However,the clear pathogenesis is still unknown.Recently,researchers believe that the major mechanism of Aplastic Anemia is dysimmunity,mostly T lymphocytes abnormalities.In addition,immunosuppressive agents are validated effective among70%patients.This fact further proves that dysimmunity plays significant roles in the pathogenesis of Aplastic Anemia.Current researches focus on regulatory T cells and Th17cells.Regulatory T cells have immunosuppressive function,low multiplication capacity.They can inhibit potentially harmful self-reactive T cells by identification of autoantigens,control the intensity of immune response,ease the tissue damage and maintain the stability of autoimmunity.Furthermore,regulatory T cells play important roles in autoimmune diseases.Many researchers found that in diverse autoimmune diseases,the amount of these cells or their function declines.Foxhead/winged-helix transprcription factor p3is one validated specific marker from CD4+CD25+Treg,which plays vital roles in both the differentiation development and function of CD4+CD25+Treg,and the development of autoimmune diseases.In addition,one cytokine IL-17secreted by novel Th17cells is also validated as an important contributor to autoimmune diseases.IL-17binds the receptor,then activated,leads to the expression and release of chemokine,stimulating factor and adhesive molecules,and thereby affects pathological processes of infection,tumor and autoimmune diseases.What’s more,IL-17is able to inhibit the proliferation of human blood progenitor cells.Cyclosporine A is a common medication for the treatment of AA.It can efficiently inhibit cellular immune response mediated by T cells,and block the proliferation and differentiation of T cells.In conclusion,regulatory T cell and cytokine Foxp3,Th17cell and IL-17A gene all play a pivotal role in the triggering and developing of aplastic anemia(AA),and Cyclosporine A(CsA),as the immunosuppressor,is considered to take effect on regulator T cell and cytokine Foxp3,Th17cell and IL-17A gene.ObjectiveTo explore the effect of Cyclosporine on regulatory T cell、oxp3and IL-17gene in the peripheral blood of children with chronic aplastic anemia,seeking the theoretical basis for the reaserch of pathogenesis and therapeutic target of aplastic anemia.Materials and MethodsFifty children with chronic aplastic anemia were collected from the Third Affiliated Hospital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University.All of them were without any treatment.Then they were divided into the cyclosporine treatment group and the non-CsA treatment groups,who received treatment for6months.Twenty healthy children from the Third Affiliated Hospital of Zhengzhou University were collected as normal controls over the same period.Therefore,the object of study can be divided into three groups:CsA treatment group(30cases),non-CsA treatment group(20cases)and normal control group(15cases).Gender,age was no significant difference among the three groups.The periods of follow-up was6months.The expression of CD4+CD25+CD127lowTreg was detected by flow cytometry and the expression of Foxp3mRNA and IL-17A mRNA was detected by Real-time Q-PCR.Results1.Expression level of CD4+CD25+CD1271ow Treg:the group with CsA treatment is5.31±1.18,which is significantly higher than the group without CsA treatment(4.56±0.95),and approximately to the control group(5.91±1.51)2.Expression level of Foxp3mRNA:there are no significant differences between CsA treatment group(1.01±0.26)and control group(1.17±0.32).However,the group without CsA treatment(0.79±0.34)shows to be significantly lower than CsA treatment group and control group.3.Expression of IL-17A mRNA:the expression level of aplastic anemia patients with CsA treatment is approximately the same with control group,and there are no significant differences between them(p>0.05);the expression level of patients without CsA treatment is significantly higher than the control group(p<0.05);In addition,the group of CsA treatment exibits significant differences with the group without CsA treatment(p<0.05).Conclusion1.CsA can increase the expression profile of CD4+CD25+CD1271ow Treg and Foxp3mRNA in peripheral blood of enfant with AA,and decrease IL-17A mRNA level.2.T regulatory cell,Foxp3and IL-17participated in the triggering and development of AA.