补体C3对同种异基因移植排斥中Th17细胞应答的调控机制研究

发布时间：2017-12-31 00:37

  本文关键词：补体C3对同种异基因移植排斥中Th17细胞应答的调控机制研究　出处：《第三军医大学》2017年博士论文　论文类型：学位论文

  更多相关文章： 同种异基因移植排斥 补体C3 Th17细胞 Tregs

【摘要】：移植是治疗器官功能衰竭的有效手段,移植排斥反应是移植物丢失的主要原因。CD4+T细胞是介导移植排斥反应的重要细胞,不同CD4+T细胞亚群在移植排斥反应中功能各不相同。Th1及Th17细胞加速移植排斥,而Th2及Treg细胞则诱导移植物耐受。目前广泛使用的免疫抑制药物,如环孢素A、FK506及雷帕霉素等,通过抑制整个T细胞亚群的增殖分化来调控移植排斥反应,存在明显的局限性。因此,发展选择性抑制T细胞亚群的新型免疫抑制剂是未来抗排斥药物研究的方向。研究移植状态下T细胞亚群分化调节机制,对于理解移植排斥反应病理生理和发展选择性干预T细胞的抗排斥反应药物具有十分重要的意义。Th17是CD4+T细胞的重要亚群,因主要分泌细胞因子IL-17得名。IL-17可向炎症部位募集大量单核细胞、中性粒细胞或与其它炎症因子共同作用参与调节免疫炎症反应。Th17细胞在过敏性哮喘、糖尿病、银屑病、SLE及移植排斥反应中具有重要作用。研究发现,Th17细胞局部浸润与移植肾功能及肾组织损伤的严重程度显著相关。运用特异性抗体阻断IL-17A,小鼠移植肺中淋巴细胞及IFN-γ阳性细胞浸润显著降低,且阻塞性支气管炎显著缓解。研究移植状态下Th17细胞分化调控机制,对开发特异性调节药物具有重要的价值。补体是天然免疫系统的重要组分。研究表明,补体参与调节T细胞增殖分化。CD4+T细胞上表达补体受体C3a R及C5a R,与补体活化产物C3a及C5a结合后,激活G蛋白下游通路,促进T细胞增殖分化及Th1细胞应答。同种异基因小鼠肾移植中补体C5a R基因缺陷显著延长移植物存活,T细胞应答明显减弱,表明同种异基因移植排斥反应中补体参与调节T细胞增殖分化。然而,同种异基因移植中补体活化是否与Th17细胞存在关联并参与调节Th17细胞增殖分化尚不清楚。补体C3是补体系统的枢纽分子。补体C3基因缺陷时,Th1/Th17细胞应答衰减,同时补体C3参与调节Treg细胞增殖分化及功能发挥,提示同种异基因移植中补体C3可能参与调节Treg/Th17细胞应答,在移植排斥反应中发挥重要作用。【研究目的】1、研究同种异基因移植过程中补体的活化及Th17细胞增殖分化的关联;2、建立同种异基因移植模型,明确补体组分C3对移植物存活及Th17细胞应答的影响;3、深入探讨补体C3对同种异基因移植排斥反应中Th17细胞应答的调控机制。【研究方法】1、同种异基因移植中补体的活化及Th17细胞的增殖分化1)收集肾移植患者外周血,分离PBMC及血清,FCM检测移植排斥过程中Th17细胞增殖分化,ELISA检测补体活化片段C3a及C5a含量,明确移植过程中补体活化情况;2)收集发生急慢性排斥反应及正常肾组织,IHC检测肾组织中补体活化、IL-17表达、T细胞浸润,免疫荧光染色IF检测排斥肾组织中Th17细胞浸润情况。3)培养人近端肾小管上皮细胞(HK2),以补体活化产物C3a刺激后,IHC检测HK2中IL-17的分泌。4)补体活化产物C5a刺激HK2后,IHC及FCM检测HK2中IL-17的分泌。2、同种异基因移植中补体组分C3对移植物存活及Th17细胞应答的影响1)Bm12,C3+/+及C3-/-小鼠尾部皮肤分别移植到Bm12小鼠背部,7天后观察移植物排斥反应,明确局部补体C3缺乏对同种异基因移植物存活的影响;2)Bm12小鼠尾部皮肤分别移植到C3+/+或者C3-/-小鼠背部,7天后观察移植物排斥反应,明确系统性补体C3缺乏对同种异基因移植物存活的影响。3)通过HE、IHC及IF染色检测移植物局部中性粒细胞、巨噬细胞、Th17细胞及DC等浸润情况,q PCR检测移植物局部炎症因子及趋化因子表达情况。4)移植不同时间点,取Bm12小鼠腋窝引流淋巴结及脾脏,FCM检测Th1/17细胞频率,明确补体C3缺陷对Th1/17细胞应答的影响。3、同种异基因移植中补体组分C3对Th17细胞应答的调节机制1)移植10天后,取Bm12小鼠腋窝引流淋巴结,MLR检测补体C3缺陷对淋巴细胞增殖的影响。2)移植不同时间点,取Bm12小鼠腋窝引流淋巴结及脾脏,FCM检测Treg细胞频率,明确在此模型中补体C3缺陷对Treg细胞应答的影响。3)利用Anti-CD25 mAb去除Treg细胞后,观察C3-/-移植物存活情况,深入探讨Treg细胞在延长C3-/-移植物存活中的重要作用。4)分离纯化Na?ve CD4+T细胞与辐照后的BMDCs共培养9-12天,收集上清检测IL-10的分泌,收集细胞通过PCR及FCM检测Treg细胞增殖分化情况。【研究结果】1、同种异基因移植中,补体大量活化及Th17细胞应答增强1)与移植前相比,同种异基因肾移植后患者血清中补体活化片段C3a及C5a浓度显著增加;发生排斥反应肾组织中补体C3、补体受体C5a R及补体活化终产物C5b-9较正常肾组织表达明显增加。2)与移植前相比,同种异基因肾移植后患者PBMCs中Th17细胞频率升高;排斥反应肾组织中Th17细胞浸润显著增加。3)与未刺激组相比,补体活化产物C3a及C5a刺激显著上调IL-17表达。2、局部补体组分C3缺陷显著延长同种异基因移植物存活时间并衰减Th17细胞应答1)来源于C3+/+移植物在移植后17天被完全排斥,与之不同的是,来源于C3-/-移植物存活时间显著延长,60%C3-/-B6移植物存活时间超过30天,表明移植物局部C3基因缺陷可延长MHC-Ⅱ不匹配同种异基因移植物存活时间。2)Bm12移植物存活时间在C3+/+及C3-/-两种小鼠间没有差异,移植物存活时间均小于14天,表明系统性C3缺陷不能延长同种异基因移植物存活时间。3)HE染色发现,C3-/-移植物组织坏死、单核细胞浸润显著减轻;IHC检测发现,C3-/-移植物中性粒细胞、巨噬细胞及T细胞浸润显著减少;IF检测发现,C3-/-移植物局部Th17细胞浸润明显减少。4)q PCR检测发现,C3-/-移植物中Th1/Th17细胞应答关键炎症因子,如细胞因子IFN-γ、IL-17及IL-23,趋化因子CXCL-9,mRNA表达显著降低。与之相似的是炎症因子IL-1β、IL-6及TNF-α在C3-/-移植物表达亦显著衰减。表明,移植物局部补体C3缺乏导致Th1/Th17细胞应答相关炎症因子及趋化因子表达降低。5)FCM检测发现,C3-/-移植物显著降低Th1/17细胞频率,表明同种异基因移植中补体C3促进Th1/17细胞应答。3、同种异基因移植排斥中,补体组分C3抑制Treg细胞增殖分化,促进Th17细胞应答,加速排斥反应发生1)MLR实验发现,补体C3基因缺陷时淋巴细胞增殖显著降低。2)PCR及IHC检测移植物中Treg细胞特异性转录因子Foxp3表达,发现C3-/-移植物中Foxp3表达显著上升,表明C3-/-移植物存活延长可能与Treg的密切相关。3)FCM检测Bm12小鼠脾脏及引流淋巴结中Treg细胞频率,发现,C3-/-移植物显著增加Treg细胞频率,表明C3-/-移植物存活延长可能依赖于Treg细胞的扩增。4)Anti-CD25 m Ab去除Treg细胞后观测C3-/-移植物存活,发现,去除Treg细胞后Th17细胞应答增强,C3-/-移植物存活时间显著缩短,排斥反应明显增强,表明Treg在促进C3-/-移植物存活延长中发挥关键作用。5)IF检测发现,C3-/-移植物中DCs浸润明显减少,共刺激分子CD80表达减弱;通过将BMDCs与Na?ve CD4+T细胞共培养,发现,与C3+/+DCs相比,C3-/-DCs能够显著促进IL-10的分泌,Foxp3表达及Tregs增殖分化,表明补体C3通过DCs抑制Tregs细胞增殖分化。【主要结论】本研究中,我们通过收集临床同种异基因肾移植标本,检测补体活化及Th17细胞增殖分化;通过体外细胞实验,检测补体活化产物对IL-17产生的影响;建立同种异基因移植模型,明确补体组分C3对移植物存活及Th17细胞应答的影响;深入探讨补体C3在同种异基因移植排斥中对Th17细胞应答的调控机制,得出主要结论如下:1、同种异基因移植过程中,补体的大量活化与Th17细胞应答紧密相关;2、同种异基因移植中,补体C3缺陷显著延长移植物的存活时间并衰减Th17细胞应答;3、同种异基因移植排斥反应中,补体组分C3抑制Tregs细胞增殖分化,促进Th17细胞应答,加速排斥反应发生。
[Abstract]:Transplantation is an effective treatment of organ failure, allograft rejection is a major cause of graft loss of.CD4+T cells is mediated rejection of transplanted cells, different subsets of CD4+T cells in allograft rejection in the different functions of.Th1 and Th17 cells accelerated allograft rejection, whereas Th2 and Treg cells inducing allograft tolerance the widely used immune suppressing drugs, such as cyclosporine A, FK506 and rapamycin, through inhibiting the proliferation and differentiation of T cell subsets in the regulation of transplant rejection, there are obvious limitations. Therefore, the development of new immunosuppressive agents selectively inhibit T cell subsets of anti rejection drugs is the future research direction of transplantation under the condition of T cell subsets differentiation regulation, to understand the pathophysiology of allograft rejection and development of selective intervention T cells anti rejection drugs with ten points To the meaning of.Th17 is important CD4+T cell subsets, mainly due to the secretion of IL-17 named.IL-17 to the site of inflammation to raise a lot of mononuclear cells, interaction of neutrophils and other inflammatory factors involved in the regulation of.Th17 cell immune inflammation in allergic asthma, diabetes, psoriasis, SLE and graft rejection is important effect of reaction. The study found that Th17 cells infiltration was significantly correlated with the severity of renal transplantation and renal tissue injury. Using specific antibodies blocking IL-17A lymphocytes and IFN- positive cell infiltration significantly reduced mice lung transplant, and relieve obstructive bronchitis. Transplantation research status of Th17 cell differentiation regulation mechanism, has the important value for the development of specific drug regulation. Complement is an important group of natural immune system. Research shows that the complement is involved in the regulation of T proliferation and differentiation in.CD cells The expression of C3a R and C5a R complement receptor on 4+T cells, binding and complement activation products of C3a and C5a after activation of G downstream pathway, promote the proliferation and differentiation of T cells and Th1 cell responses. Allogeneic mouse kidney transplantation R complement C5a gene defects significantly prolonged graft survival, T cell response was reduced, show that the same allogeneic transplantation rejection complement is involved in the regulation of proliferation and differentiation of T cells. However, allogeneic transplantation of Th17 cells and complement activation is associated and involved in the regulation of proliferation and differentiation of Th17 cells is not clear. C3 is the hub of the complement molecule of the complement system. Complement C3 gene defects, Th1/Th17 cell response attenuation, and complement C3 participation Treg regulates the differentiation and function of cell proliferation play, suggesting that allogeneic transplantation of complement C3 may be involved in the regulation of Treg/Th17 cell responses in allograft rejection and play an important role [research. The purpose of] 1, the complement of allogeneic transplantation and the activation of Th17 cell proliferation and differentiation related; 2, the establishment of allogeneic transplantation model, clear complement component C3 effect on graft survival and Th17 cell responses; 3, to further study the mechanism of regulation of complement C3 allogeneic transplantation rejection in Th17 cells in response. [Methods] 1 allogeneic transplantation of complement activation and proliferation and differentiation of Th17 cell 1) collected the peripheral blood of patients with renal transplantation, separation of PBMC and serum FCM detection, graft rejection in the process of proliferation and differentiation of Th17 cells, C3a and C5a in the detection of ELISA fragment of complement activation, clear the transplantation process in the case of complement activation; 2) were collected in acute and chronic rejection and normal renal tissue, complement activation, renal tissue to detect IHC IL-17 expression in T cells, immunofluorescence staining to detect IF rejection in renal tissue of Th17 cell infiltration .3) in cultured human proximal tubular epithelial cells (HK2), product of C3a stimulation to complement activation, secretion of.4 IL-17 IHC HK2) in the detection of complement activation product C5a after HK2 stimulation, IL-17 IHC and FCM HK2 detection in the secretion of.2, allogeneic transplantation in the C3 group complement effect on graft survival and Th17 cell response 1) Bm12, C3+/+ and C3-/- mice tail skin were transplanted into Bm12 mice, 7 days after the observation of graft rejection, clear local complement C3 deficiency plant survival effect on allogeneic; 2) Bm12 mice tail skin grafting respectively to C3+/+ or C3-/- mice after 7 days. Observation of graft rejection, a clear system of complement C3 deficiency on allogeneic allografts by HE.3), to detect local grafts of neutrophils, IHC and IF staining of macrophages, Th17 cells and DC infiltration, Q detection of PCR graft The expression of.4 local inflammatory cytokines and chemokines) transplantation at different time points, the Bm12 mice axillary draining lymph node and spleen, FCM detection of Th1/17 cell frequency, clear complement C3 defects affect Th1/17 cell responses to.3, allogeneic transplantation group complement C3 on Th17 cell response mechanisms regulating 1) transplantation 10 days later, Bm12 mice were sacrificed and axillary lymph node dissection, MLR detection of complement C3 defect effect on lymphocyte proliferation.2) transplantation at different time points, the Bm12 mice axillary draining lymph node and spleen, FCM detection of Treg cell frequency, clear complement C3 defects in this model of Treg cell responses to.3 cells by removal of Treg) Anti-CD25 mAb, C3-/- to observe the graft survival situation, in-depth study of Treg cells in the extended C3-/- shift.4 an important role in the survival of plants) separation and purification of Na? Ve and CD4+T cells after irradiation BMDCs were cultured for 9-12 days, collect Supernatant from detection of IL-10, PCR and FCM cells were collected by detection of Treg cell proliferation and differentiation. [results] 1, allogeneic transplantation, a large number of complement activation and Th17 cell response increased 1) compared with before transplantation, allogeneic renal transplantation serum complement activation fragment C3a and C5a were significantly the increase in renal tissue rejection; complement C3, activation of complement receptor C5a R and complement the end product C5b-9 compared with normal renal tissue was significantly increased compared with.2) before transplantation, allogeneic Th17 cell frequency after renal transplantation in patients with PBMCs increased; Th17 cells were significantly increased.3 rejection in renal tissue compared with) no stimulation group, complement activation products C3a and C5a stimulation significantly up-regulated the expression of IL-17.2, local complement component C3 defects significantly prolong the allograft survival time and attenuation of Th17 cell response 1) derived from C3+/+ Plants in 17 days after transplantation was completely excluded, and the difference is derived from the C3-/- graft survival time was significantly prolonged, 60%C3-/-B6 grafts survived more than 30 days, showed that the graft local C3 gene MHC- II does not match the defects can prolong the allograft survival time.2 Bm12) graft survival time in C3+/+ C3-/- and no differences between the two types of mice, the survival time of the grafts were less than 14 days, C3 shows that the system defects cannot prolong allograft survival time.3) HE staining showed that C3-/- graft tissue necrosis, infiltration of mononuclear cells significantly reduced; IHC assay showed that C3-/- graft neutrophils, macrophages and T cells were significantly decreased; IF assay showed that C3-/- graft local infiltration of Th17 cells significantly reduced.4) found Q PCR detection, C3-/- shift key inflammatory cytokines Th1/Th17 cell responses in plants, such as cytokines IFN-, IL-17 and IL-23, chemokine CXCL-9, mRNA expression was significantly reduced. Similar inflammatory cytokine of IL-1, IL-6 and TNF- alpha graft expression was also significantly attenuated in C3-/-. The graft showed that local complement C3 deficiency related inflammatory cytokines Th1/Th17 cell response and chemokine expression decreased FCM detection,.5) the C3-/- graft significantly reduced the frequency of Th1/17 cells, showed that allogeneic transplantation of complement C3 promotes Th1/17 cell responses to.3, allograft rejection, complement component C3 inhibited Treg cell proliferation and differentiation, promote Th17 cell response, accelerated rejection occurred in 1) MLR experiments found that complement C3 gene defects in lymphocyte proliferation significantly.2 PCR and IHC) to reduce the detection of Treg cells in grafts specific transcription factor Foxp3 expression, C3-/- graft Foxp3 expression was significantly increased, showed that C3-/- and Treg could prolong graft survival closely .3) FCM detection of Bm12 in mouse spleen and draining lymph nodes of Treg cell frequency, found that C3-/- graft significantly increased frequency of Treg cells, C3-/- showed that the graft survival may depend on the Treg cells was.4 Anti-CD25 m Ab) removal of Treg cells after observing C3-/- graft survival, found that the removal of Treg cells after Th17 cells increased response C3-/- graft survival time was significantly shortened, the rejection was significantly enhanced, showed that Treg in promoting C3-/- graft survival play a key role in the.5 extension) IF detection, C3-/- graft DCs infiltration was significantly reduced, the costimulatory molecule CD80 expression decreased by BMDCs and Na; ve? CD4+T cells were co cultured. Found that, compared with C3+/+DCs, C3-/-DCs can significantly promote the secretion of IL-10, Foxp3 and Tregs showed that the expression of proliferation and differentiation, complement C3 inhibits the proliferation and differentiation of Tregs cells by DCs. [] the main conclusions in this study, I Through the collection of clinical allogeneic renal transplantation specimens, detection of complement activation and proliferation and differentiation of Th17 cells; in vitro, affect the detection of complement activation products of IL-17; the establishment of allogeneic transplantation model, clear complement component C3 effect on graft survival and Th17 cell responses in the same study; complement C3 allogeneic transplantation rejection on Th17 cell response mechanism, main conclusions are as follows: 1, the process of allogeneic transplantation, complement activation is closely related with the immune response of Th17 cells; 2, allogeneic gene transplantation, complement C3 deficiency significantly prolong graft survival time and attenuation of Th17 cell response; 3 allogeneic transplantation, rejection, complement component C3 inhibited Tregs cell proliferation and differentiation, promote Th17 cell response, accelerated rejection.

【学位授予单位】：第三军医大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R392.4

【相似文献】

相关期刊论文 前10条

1 任志刚;蒋建文;Valujskikh A;Baldwin Ⅲ WM;Fairchild RL;;同种异基因移植中T细胞应答的研究进展[J];中华移植杂志(电子版);2010年03期

2 徐苗;;利用早期B细胞应答检测技术进行新型疫苗免疫原的快速追踪筛选[J];国际生物制品学杂志;2006年03期

3 王桂秋;;对甲型流感疫苗接种的人体细胞毒性T细胞应答[J];国外医学.生物制品分册;1982年02期

4 刘凤玲,陈政良;C3与T细胞应答的研究进展[J];细胞与分子免疫学杂志;2005年S1期

5 肇静娴;曾耀英;江逊;季煜华;刘毅;;人胎盘绒毛提取物体外对T细胞应答的抑制效应[J];第四军医大学学报;2006年12期

6 张珏;谭雨龙;杨菲;朱波;;肿瘤环境影响抗感染CD8~+T细胞应答启动的初步研究[J];免疫学杂志;2013年03期

7 鲁加龙;;接种曼氏血吸虫疫苗小鼠的局部淋巴器官细胞应答的表型分析[J];国外医学(寄生虫病分册);1991年04期

8 丁传林;树突状细胞的发育、亚群及其对T细胞应答类型的调控[J];上海免疫学杂志;2002年05期

9 唐漾波;唐小平;金侠;;人类免疫缺陷病毒1型特异性CD8~+T细胞应答中人类白细胞抗原Ⅰ的限制位点[J];中华传染病杂志;2007年09期

10 裘辉;涂永久;李小凤;韩健;梁华平;;创伤小鼠骨髓来源树突状细胞诱导T细胞应答的能力变化[J];第四军医大学学报;2009年09期

相关会议论文 前10条

1 唐裕杰;蒋廷旺;韩志君;周晔;孙懿;邓安梅;仲人前;;原发性胆汁性肝硬化患者Th17细胞培养与纯化[A];全国临床免疫检验研讨会暨第六届全国临床免疫学术会议论文汇编[C];2009年

2 应琳;李和权;周建英;;Th17细胞在阻塞性睡眠呼吸暂停低通气综合征中作用的研究[A];中华医学会呼吸病学年会——2013第十四次全国呼吸病学学术会议论文汇编[C];2013年

3 周运恒;荣光华;熊怡松;朱烨;耿红莲;杨再兴;仲人前;;原发性胆汁性肝硬化病人血清中Th17相关细胞因子的变化[A];第六届全国免疫学学术大会论文集[C];2008年

4 荣光华;周运恒;仲人前;;主要Th17相关细胞因子在原发性胆汁性肝硬化患者血清水平及其意义[A];中华医学会第七次全国检验医学学术会议资料汇编[C];2008年

5 杨洵哲;张婷;王立;孔芳;张奉春;;Th17细胞与调节性T细胞平衡在原发性胆汁性肝硬化发病机制中的作用初探[A];第17次全国风湿病学学术会议论文集[C];2012年

6 裘辉;涂永久;李小凤;韩健;梁华平;;创伤小鼠骨髓来源的树突状细胞诱导T细胞应答的能力降低[A];2009年全国危重病急救医学学术会议论文汇编[C];2009年

7 张景博;马道新;朱效娟;曲迅;彭军;纪春岩;侯明;;Th17、Th1和Tc1细胞亚群在免疫性血小板减少性紫癜患者中的变化及意义[A];第12届全国实验血液学会议论文摘要[C];2009年

8 韩丽娜;张亚晶;杨庭树;郭树理;;自身免疫性心肌炎大鼠Th1、Th2、Th17亚群免疫反应状态[A];中国病理生理学会第九届全国代表大会及学术会议论文摘要[C];2010年

9 李红梅;何庆南;李晓燕;帅兰军;周频;易著文;;槐杞黄对哮喘大鼠Th1、Th2、Th17表达及肺泡巨噬细胞吞噬功能的影响[A];中华医学会第七届全国哮喘学术会议暨中国哮喘联盟第三次大会论文汇编[C];2010年

10 王敏;李先平;伍婷;;重组金黄色葡萄球菌肠毒素C3生物学活性的初步研究[A];中华医学会第七次全国中青年检验医学学术会议论文汇编[C];2012年

相关重要报纸文章 前10条

1 ;实达：以“C3”修正“3C”[N];中国电子报;2003年

2 本报记者 陈礼明;实达：从“3C”到“C3”[N];中国高新技术产业导报;2003年

3 本报记者 赵守民　通讯员 王文山;高铁C3技术的领航者[N];中国铁道建筑报;2011年

4 王恩泽;将C3预警监控系统打造成信贷“防火墙”[N];中国城乡金融报;2012年

5 段文利 谢静;谁在艾滋病进程中“垂帘听政”[N];健康报;2006年

6 通讯员汪春雨;农业银行启动C3全行宣讲活动[N];中国城乡金融报;2012年

7 张馨;C3型集装箱平车进入澳洲市场[N];人民铁道;2007年

8 未名;节能环保王 威盛 C3处理器冷静成就一切[N];电脑商报;2005年

9 ;雪铁龙C3：永远与众不同[N];中国商报;2003年

10 本报记者顾水根 通讯员张明丽;兵团分行完善C3系统应用机制[N];中国城乡金融报;2013年

相关博士学位论文 前10条

1 郑权友;补体C3对同种异基因移植排斥中Th17细胞应答的调控机制研究[D];第三军医大学;2017年

2 缪金林;CD147分子调控Th17细胞应答介导类风湿关节炎发病机制的研究[D];第四军医大学;2016年

3 钟茂华;可溶性HLA-G二聚体抑制同种T细胞应答的研究[D];华中科技大学;2008年

4 吴莉;调节IL-7/IL-7R信号通路抑制原因不明性复发性流产模型中Th17细胞的炎性作用机制研究[D];安徽医科大学;2015年

5 张敏;JAK/STAT5信号通路在Th17细胞介导的中性粒细胞哮喘小鼠模型中作用的研究[D];广西医科大学;2016年

6 周恍;重庆市某社区10年糖尿病患病率变化趋势分析及补体C3和脂多糖结合蛋白对2型糖尿病发生的预测价值研究[D];重庆医科大学;2015年

7 李静;Th17细胞在骨髓增生异常综合征发病机制中的作用[D];天津医科大学;2016年

8 张文君;HIV感染中Th17细胞与消化道上皮屏障完整性关系的实验研究[D];中国疾病预防控制中心;2015年

9 谭雨龙;补体C3在李斯特菌感染模型中调节CD8~+T细胞应答收缩和记忆形成[D];第三军医大学;2014年

10 师天燕;原发性胆汁性肝硬化患者的临床特点及Th17细胞在发病中作用的研究[D];北京协和医学院;2013年

相关硕士学位论文 前10条

1 李微;NAFLD小鼠Th17通路变化及白藜芦醇作用机制的初步探讨[D];河北医科大学;2015年

2 黄香丽;1型糖尿病与Th17细胞及其相关细胞因子关系的初步研究[D];青海大学;2015年

3 周鑫;网络化控制器的设计及在C3加氢反应的应用[D];北京化工大学;2015年

4 郭帅博;铁催化吲哚C3位官能团化反应的研究[D];兰州大学;2015年

5 周玉荣;Th17细胞与自身免疫性甲状腺疾病研究进展[D];蚌埠医学院;2015年

6 杨婷;盆腔炎性疾病后遗症患者31例中药灌肠治疗前后C3、C4表达分析[D];成都中医药大学;2015年

7 朱丽丽;潍坊城市道路西北片区C3工程项目风险管理研究[D];中国海洋大学;2015年

8 柏社香;Th17细胞、IL-17、IL-6与食管癌的相关性研究[D];东南大学;2015年

9 钟燕明;PBC患者外周血25-(OH)D_3、Th17细胞、CD4~+Treg细胞的变化及意义[D];山西医科大学;2016年

10 孙晓仙;GC-MSC诱导Treg、Th17细胞的作用及机制[D];江苏大学;2016年

，

本文编号：1357274