树突状细胞和动脉粥样硬化-文献抄读.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,Dendritic cells(DCs)and atherosclerosis,Introduction,Of DCs,Initially described in the skin by Langerhans in 1868,dendritic cells(DCs)were identified as antigen-presenting cells in 1973 by the pioneering work of Steinman and Cohn.In all tissues and all pathological conditions,DCs are minor cell populations but they are the most potent antigen-presenting cells.,Origin,migratory routes of DCs,The general concept on the life cycle of DCs involves three stages.They originate from haematopoietic stem cells in the bone marrow and,circulate as precursors in the blood stream,taking,residence in target tissues at sites of potential antigen entry.,Within these tissues,they give rise to immature interstitial DCs that act as sentinels,which continuously and efficiently sample the antigenic content of their microenvironment.,In the steady state,immature DCs capture harmless self-antigens in the absence of inflammatory signals.They might enter the regional lymphnodes to present the self-antigen to naive or resting T cells,which will be deleted by the induction of apoptosis,silenced by the induction of anergy or primed to become regulatory T cells(Tregs).,In contrast,when infection and tissue damage occurs,immature DCs take up antigens in the presence of inflammatory signals,which cause activation and functional transformation into mature DCs,there by down regulating endocytotic capacity and upregulating chemokine receptors(e.g.,CCR-7),adhesion(e.g.,CD50)and activation molecules needed for antigen presentation(e.g.,CD83,CD86).,pDCs(0.2%among leukocytes)express BDCA-2(=CD303)and CD123,and are specialized in innate antiviral immune responses by producing copious amounts of type I interferons upon exposure of intracellular TLR9 and TLR7 to DNA and RNA,viruses,respectively.,Apart from responding to different pathogen associated molecular patterns(PAMPs)and,secreting different cytokines,mDCs and pDCs also differ in migration behaviour.Generally it is assumed that mDCs are the conventional DCs that infiltrate,peripheral tissues while pDCs migrate directly from the blood into lymphoid organs.,DCs in atherosclerosis,It is important to note that DCs are actually present in healthy arteries and have been documented in the subendothelial space and at the media-adventitia junction.The localization of DCs adjacent to the vasa vasorum allows for the monitoring of important access pathways to the vessel wall,to present autoantigens such as oxidized LDL CD4+T cells,and to locally initiate inflammatory responses.,Interestingly,DCs and T cells are arrayed in clusters that primarily locate to the shoulder and rupture prone regions of the plaque.Importantly,it has been shown that patients with angina and acute MI have reduced circulating blood-derived DC precursors.In fact,blood derived DCs and plasmacytoid DCs are actually diminished in patients with documented CAD potentially due to increased recruitment to plaques.,DCs were shown to be present in human unstable plaques and higher DC densities were found in carotid plaques from symptomatic patients as compared to those from asymptomatic patients.DCs were also described in human symptomatic in-stent and in aortic aneurysms.The above studies suggest that the presence of DCs is associated with progression of atherosclerosis.,A recent study sheds light on the possible role that PDCs may exhibit.Administration of 120G8 mAb(antibody which recognizes PDCs)in LDLR,/,mice led to PDC depletion resulting in plaque T-cell accumulation and enhanced plaque progression.The authors concluded that PDCs may play a protective role in atherosclerosis,possibly by dampening T-cell proliferation and activity in peripheral lymphoid.,Concluding remarks,DCs are present in their immature forms in non-diseased arteries and become activated during atherogenesis.Some DCs cluster with T cells directly within atherosclerotic lesions,while others migrate to lymphoid organs to activate T cells.,