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The Research On The Relevance Between Interleukin-23 Interleukin-17 And Transplantation Immunity

Posted on:2010-06-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:G S DuFull Text:PDF
GTID:1114360275952975Subject:Surgery
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Objective:To probe the changes of interleukin23(IL-23) and interleukinl 7(IL-17) in the peripheral circulation and the pathological tissues and organ after the skin transplantation in mice;to disscuss the interaction during IL-23,IL-17 and regulatory T cells under the situation of different immune state;to understand the effect of immulogical regulation of IL-23/IL-17 axis after the skin transplantation in mice and to provide the guidance of the theory for the prevention,diagnosis,treatment and immune tolerance of rejection after transplantation in clinic.Method:The construction of animal model of skin transplantation in mice(n=10): groupl,isotransplantation(BALB/c→BALB/c);group2,allotransplantation (C57BL/6→BALB/c);group3,the donor spleenocytes were transfused to the recipient before transplantation(C57BL/6→BALB/c).To observe the three groups appearance changes of the transplanted skin and the pathological sections difference with Hematoxylin-eosine(HE) at different timing;to detect the concentration of IL-17,IL-23 in blood serum with ELISA method,IL-23mRNA,IL-17mRNA with R-T-PCR and Tregs in spleen with Flow cytometry.Result:With the observation and sections of H.E:the transplanted skin is well in the isotransplantation group without acute rejection,the typical acute rejection was occurred in the allotransplantation group and the rejection was significantly reduce in the group of preoperative infusion of allogeneic spleen cells in mice.There is no statistical significance in three groups among IL-17,IL-23,IL-23mRNA and IL-17mRNA at the first day after skin transplantation in mice(P>0.05);to compare group2,group 3 with the groupl,there is statistical significance with the expressions of IL-23,IL-23mRNA at the 3,5,7 day(P<0.01) and at the same time there is no statistical significance between 2rd and 3th group(P>0.05);with the expressions of IL-17,IL-17mRNA,there is also significant difference between group2 and group1 or 3,and no statistical significance between 1 and 3 group at 3,5,7day after skin transplantation(P<0.01).The percentage of CD4~+FoxP3+Treg account for CD4+T of the three groups is (0.9±0.6)%,(0.7±0.5)%,(0.8±0.4)%respectively at 1 day after transplantation and no statistical significance of three groups(P>0.05).At the 7 day,the percentage of 3 group is higer than that of 2 group,(5.1±2.8)%,(4.54±2.5)%respectively with statistically significant(p=0.00);the relative value of Th17/CD4~+FoxP3+Treg in the 2 group is higer than that in the 3 group(p=0.00).Conclusion:1.Early post-transplant acute rejection occurs,expression of IL-23,IL-17 and IL-23mRNA,IL-17mRNA is in high-level;under conditions of no rejection and immune tolerance,IL-23,IL-17 and IL-23mRNA,IL-17mRNA rise in early stage,reducing its value as reduced inflammation,IL-23,IL-17 could serve as a preditor of acute rejection and prognostic indicator.2.In the acute rejection model,IL-23 and IL-17 expression was positively correlated.As the upper reaches of the IL-17 factor,IL-23 regulates Th17 cell growth and its secretion of IL-17.Inhibition of IL-23 may reduce IL-17 production,which might decrease the incidence of rejection.3.Infusion of donor spleen cells,can induce immune tolerance in skin allograft recipient mice.The mechanism may be related to the reduction of IL-17 and the increase of CD4+FoxP3+Tregs.4.Infusion of donor spleen cells may stimulate the generation of CD4+FoxP3+ Tregs in skin allograft recipient mice.Th17/CD4+FoxP3+Treg ratio may affect the immune system after transplantation.
Keywords/Search Tags:acute rejection, IL-23, IL-17, CD4~+FoxP3~+Tregs
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