Recombinant interleukin-33(IL-33)inhibits tumor growth,but the detailed immunological mechanism is still unknown.IL-33-mediated tumor suppression did not occur in Batf3^(−/−)mice,indicating that conventional type 1 de...Recombinant interleukin-33(IL-33)inhibits tumor growth,but the detailed immunological mechanism is still unknown.IL-33-mediated tumor suppression did not occur in Batf3^(−/−)mice,indicating that conventional type 1 dendritic cells(cDC1s)play a key role in IL-33-mediated antitumor immunity.A population of CD103^(+)cDC1s,which were barely detectable in the spleens of normal mice,increased significantly in the spleens of IL-33-treated mice.The newly emerged splenic CD103^(+)cDC1s were distinct from conventional splenic cDC1s based on their spleen residency,robust effector T-cell priming ability,and surface expression of FCGR3.DCs and DC precursors did not express Suppressor of Tumorigenicity 2(ST2).However,recombinant IL-33 induced spleen-resident FCGR3^(+)CD103^(+)cDC1s,which were found to be differentiated from DC precursors by bystander ST2+immune cells.Through immune cell fractionation and depletion assays,we found that IL-33-primed ST2^(+)basophils play a crucial role in the development of FCGR3^(+)CD103^(+)cDC1s by secreting IL-33-driven extrinsic factors.Recombinant GM-CSF also induced the population of CD103^(+)cDC1s,but the population neither expressed FCGR3 nor induced any discernable antitumor immunity.The population of FCGR3^(+)CD103^(+)cDC1s was also generated in vitro culture of Flt3L-mediated bone marrow-derived DCs(FL-BMDCs)when IL-33 was added in a pre-DC stage of culture.FL-BMDCs generated in the presence of IL-33(FL-33-DCs)offered more potent tumor immunotherapy than control Flt3L-BMDCs(FL-DCs).Human monocyte-derived DCs were also more immunogenic when exposed to IL-33-induced factors.Our findings suggest that recombinant IL-33 or an IL-33-mediated DC vaccine could be an attractive protocol for better tumor immunotherapy.展开更多
目的:观察正畸力作用下牙周炎大鼠垂直吸收牙槽骨改建,探讨正畸治疗对牙周改建的可能机制。方法:将60只雄性成年Wistar大鼠随机分为3组,每组20只。A组正常加力组,B组建立牙周炎垂直骨吸收模型,C组在牙周炎垂直型骨吸收模型上加力。分别...目的:观察正畸力作用下牙周炎大鼠垂直吸收牙槽骨改建,探讨正畸治疗对牙周改建的可能机制。方法:将60只雄性成年Wistar大鼠随机分为3组,每组20只。A组正常加力组,B组建立牙周炎垂直骨吸收模型,C组在牙周炎垂直型骨吸收模型上加力。分别于加力第1、3、7、14、21天处死大鼠,取第一磨牙近中牙槽骨进行组织形态学、逆转录聚合酶链反应(qRT-PCR)和蛋白质免疫印迹(Western Blot)检测。结果:正畸加力后大鼠垂直吸收侧逐渐出现牙周膜纤维排列紊乱,破骨细胞逐渐增加,至加力第14天后破骨细胞生成逐渐减少,牙周纤维排列趋于稳定,出现新骨沉积。C组在加力后第14天白细胞介素-33(interleukin-33,IL-33)mRNA、活化T细胞核因子c1(nuclear factor of activated T cells c1,NFATc1)mRNA以及IL-33、NFATc1蛋白相对表达量达峰值,高于B组和A组(P<0.05),之后表达逐渐下降。结论:对于牙周炎伴垂直吸收大鼠,在积极控制炎症和咬合创伤后,实施正畸力可调整牙槽骨吸收和沉积,促进牙槽骨改建。正畸力可促使IL-33、NFATc1表达上调,进而参与牙周膜改建过程。展开更多
基金the National Research Foundation of Korea(SRC-2017R1A5A1014560). This work was supported by grants from the National Research Foundation of Korea(SRC-2017R1A5A1014560)。
文摘Recombinant interleukin-33(IL-33)inhibits tumor growth,but the detailed immunological mechanism is still unknown.IL-33-mediated tumor suppression did not occur in Batf3^(−/−)mice,indicating that conventional type 1 dendritic cells(cDC1s)play a key role in IL-33-mediated antitumor immunity.A population of CD103^(+)cDC1s,which were barely detectable in the spleens of normal mice,increased significantly in the spleens of IL-33-treated mice.The newly emerged splenic CD103^(+)cDC1s were distinct from conventional splenic cDC1s based on their spleen residency,robust effector T-cell priming ability,and surface expression of FCGR3.DCs and DC precursors did not express Suppressor of Tumorigenicity 2(ST2).However,recombinant IL-33 induced spleen-resident FCGR3^(+)CD103^(+)cDC1s,which were found to be differentiated from DC precursors by bystander ST2+immune cells.Through immune cell fractionation and depletion assays,we found that IL-33-primed ST2^(+)basophils play a crucial role in the development of FCGR3^(+)CD103^(+)cDC1s by secreting IL-33-driven extrinsic factors.Recombinant GM-CSF also induced the population of CD103^(+)cDC1s,but the population neither expressed FCGR3 nor induced any discernable antitumor immunity.The population of FCGR3^(+)CD103^(+)cDC1s was also generated in vitro culture of Flt3L-mediated bone marrow-derived DCs(FL-BMDCs)when IL-33 was added in a pre-DC stage of culture.FL-BMDCs generated in the presence of IL-33(FL-33-DCs)offered more potent tumor immunotherapy than control Flt3L-BMDCs(FL-DCs).Human monocyte-derived DCs were also more immunogenic when exposed to IL-33-induced factors.Our findings suggest that recombinant IL-33 or an IL-33-mediated DC vaccine could be an attractive protocol for better tumor immunotherapy.
文摘目的:观察正畸力作用下牙周炎大鼠垂直吸收牙槽骨改建,探讨正畸治疗对牙周改建的可能机制。方法:将60只雄性成年Wistar大鼠随机分为3组,每组20只。A组正常加力组,B组建立牙周炎垂直骨吸收模型,C组在牙周炎垂直型骨吸收模型上加力。分别于加力第1、3、7、14、21天处死大鼠,取第一磨牙近中牙槽骨进行组织形态学、逆转录聚合酶链反应(qRT-PCR)和蛋白质免疫印迹(Western Blot)检测。结果:正畸加力后大鼠垂直吸收侧逐渐出现牙周膜纤维排列紊乱,破骨细胞逐渐增加,至加力第14天后破骨细胞生成逐渐减少,牙周纤维排列趋于稳定,出现新骨沉积。C组在加力后第14天白细胞介素-33(interleukin-33,IL-33)mRNA、活化T细胞核因子c1(nuclear factor of activated T cells c1,NFATc1)mRNA以及IL-33、NFATc1蛋白相对表达量达峰值,高于B组和A组(P<0.05),之后表达逐渐下降。结论:对于牙周炎伴垂直吸收大鼠,在积极控制炎症和咬合创伤后,实施正畸力可调整牙槽骨吸收和沉积,促进牙槽骨改建。正畸力可促使IL-33、NFATc1表达上调,进而参与牙周膜改建过程。
