国际免疫学杂志
國際免疫學雜誌
국제면역학잡지
INTERNATIONAL JOURNAL OF IMMUNOLOGY
2015年
2期
129-133
,共5页
间充质干细胞%实验性自身免疫性脑脊髓炎%CD4+ Foxp3+ Treg细胞%免疫调节
間充質榦細胞%實驗性自身免疫性腦脊髓炎%CD4+ Foxp3+ Treg細胞%免疫調節
간충질간세포%실험성자신면역성뇌척수염%CD4+ Foxp3+ Treg세포%면역조절
Mesenchymal stem cell%Experimental autoimmune encephalomyelitis%CD4 + Foxp3 + Treg cells%Immunoregulation
目的 探讨间充质干细胞(MSC)治疗自身免疫性脑脊髓炎(EAE)的机制.方法 用MOG35-55肽和弗氏完全佐剂乳化剂诱导建立C57BL/6小鼠的EAE模型;分离纯化培养骨髓来源MSC细胞;临床评分和脊髓组织切片评估小鼠的发病情况;酶联免疫吸附试验(ELISA)检测EAE组,MSC治疗组和对照组小鼠外周血细胞因子TNF-α,IFN-γ,IL-4和TGF-β的含量;流式细胞术分析3组小鼠脾脏细胞中CD4+ Foxp3+调节性T细胞(Treg)的比例变化.结果 分离纯化C57BL/6小鼠MSC成功;MSC治疗组小鼠的临床评分明显降低,且脊髓组织切片显示T细胞浸润显著减少;外周血中细胞因子IL-4,TGF-β显著高于对照组(t=7.719、17.17,P均＜0.01)和EAE组(t=54.45、48.36,P均＜0.01),IFN-γ,TNF-α低于对照组(t=104.90、1.998,P均＜0.01)和EAE组(t=270.1、13.58,P均＜0.01);脾脏细胞中CD4+ Foxp3+ Treg细胞的比例明显高于对照组(t=15.91,P＜0.01)和EAE组(t=33.39,P＜0.01).结论 MSC能够有效改善EAE小鼠的症状;其对EAE小鼠的治疗作用是通过上调抗炎细胞因子(IL-4,TGF-β)和Treg细胞并下调促炎因子(IFN-γ,TNF-α)的水平,来发挥免疫调节作用.
目的 探討間充質榦細胞(MSC)治療自身免疫性腦脊髓炎(EAE)的機製.方法 用MOG35-55肽和弗氏完全佐劑乳化劑誘導建立C57BL/6小鼠的EAE模型;分離純化培養骨髓來源MSC細胞;臨床評分和脊髓組織切片評估小鼠的髮病情況;酶聯免疫吸附試驗(ELISA)檢測EAE組,MSC治療組和對照組小鼠外週血細胞因子TNF-α,IFN-γ,IL-4和TGF-β的含量;流式細胞術分析3組小鼠脾髒細胞中CD4+ Foxp3+調節性T細胞(Treg)的比例變化.結果 分離純化C57BL/6小鼠MSC成功;MSC治療組小鼠的臨床評分明顯降低,且脊髓組織切片顯示T細胞浸潤顯著減少;外週血中細胞因子IL-4,TGF-β顯著高于對照組(t=7.719、17.17,P均＜0.01)和EAE組(t=54.45、48.36,P均＜0.01),IFN-γ,TNF-α低于對照組(t=104.90、1.998,P均＜0.01)和EAE組(t=270.1、13.58,P均＜0.01);脾髒細胞中CD4+ Foxp3+ Treg細胞的比例明顯高于對照組(t=15.91,P＜0.01)和EAE組(t=33.39,P＜0.01).結論 MSC能夠有效改善EAE小鼠的癥狀;其對EAE小鼠的治療作用是通過上調抗炎細胞因子(IL-4,TGF-β)和Treg細胞併下調促炎因子(IFN-γ,TNF-α)的水平,來髮揮免疫調節作用.
목적 탐토간충질간세포(MSC)치료자신면역성뇌척수염(EAE)적궤제.방법 용MOG35-55태화불씨완전좌제유화제유도건립C57BL/6소서적EAE모형;분리순화배양골수래원MSC세포;림상평분화척수조직절편평고소서적발병정황;매련면역흡부시험(ELISA)검측EAE조,MSC치료조화대조조소서외주혈세포인자TNF-α,IFN-γ,IL-4화TGF-β적함량;류식세포술분석3조소서비장세포중CD4+ Foxp3+조절성T세포(Treg)적비례변화.결과 분리순화C57BL/6소서MSC성공;MSC치료조소서적림상평분명현강저,차척수조직절편현시T세포침윤현저감소;외주혈중세포인자IL-4,TGF-β현저고우대조조(t=7.719、17.17,P균＜0.01)화EAE조(t=54.45、48.36,P균＜0.01),IFN-γ,TNF-α저우대조조(t=104.90、1.998,P균＜0.01)화EAE조(t=270.1、13.58,P균＜0.01);비장세포중CD4+ Foxp3+ Treg세포적비례명현고우대조조(t=15.91,P＜0.01)화EAE조(t=33.39,P＜0.01).결론 MSC능구유효개선EAE소서적증상;기대EAE소서적치료작용시통과상조항염세포인자(IL-4,TGF-β)화Treg세포병하조촉염인자(IFN-γ,TNF-α)적수평,래발휘면역조절작용.
Objective To investigate the mechanism of mesenchymal stem cells (MSC) ameliorating experimental autoimmune encephalomyelitis (EAE).Methods EAE model of C57BL/6 mice were established by the administration of MOG35-55/CFA emulsion.MSCs were purified from bone marrow of C57BL/6 mice and cultured.Then we recorded the clinical score and analyzed the pathological change of spinal cord to evaluate the state of EAE.The levels of TNF-α,IFN-γ,IL-4,and TGF-β cytokines in peripheral blood were evaluated by ELISA in EAE group,MSC-treated group,and the control group.CD4 + Foxp3 + Treg cells in these three groups were analyzed by flow cytometry.Results MSC were successfully purified and cultured.The clinical score and T-cell infiltration in spinal cord of MSC-treated mice reduced significantly.IL-4 and TGF-β in peripheral blood of the MSC-treated mice were obviously higher than those in control group(t =7.719、17.17,P ＜0.01) and EAE group(t =54.45、48.36,P ＜0.01),while IFN-γ and TNF-α were significantly lower than those in control group (t =104.90、1.998,P ＜ 0.01) and EAE group (t =270.10、13.58,P ＜ 0.01).The percent of CD4 + Foxp3 + Treg cells in spleen in the MSC-treated group was higher than that in control group (t =15.91,P ＜ 0.01) and EAE group(t =33.39,P ＜0.01).Conclusion The transplantation MSC can effectively improve the condition of experimental autoimmune encephalomyelitis.MSC performs the function of immunoregulation on EAE through up-regulating the anti-inflammatory cytokines (IL-4,TGF-β) and Treg cells and down-regulating the proinflammatory cytokines (IFN-γ,TNF-α).
