Role Of Dendritic Cell Surface Costimulatory Molecule OX40L In Vascular Inflammatory Disease And Its Mechanism

Inflammatory diseases are common diseases in human life that bring serious harm to human health,and therefore have drawn increasingly more attention.Inflammation is closely related to the pathogenesis and prognosis of cardiovascular diseases.Coronary atherosclerosis,a common cardiovascular disease,is a chronic inflammatory process.As one of the inflammatory indicators of the disease,OX40L(OX40 ligand)(CD134),belongs to type I transmembrane glycoprotein,and is mainly expressed on the surface of activated antigen-presenting cell.Dendritic cells(DCs)are the main antigen-presenting cells in vivo.Therefore,intervention in the OX40L/OX40 pathway in DC is likely to become a new approach for the prevention and treatment of coronary vascular inflammatory diseases.However,compared with other organs,mouse vascular tissue cells are rare to obtain,let alone the immune cells inside,which greatly hinders the study of vascular inflammation and its pathogenesis.In this Master’s project,I successfully created both acute(LPS intravenous injection)and chronic(atherosclerosis)animal models of vascular inflammation,and found a new method to extract enough immune cells from a limited number of mice to make single-cell suspension for flow analysis following continuous exploration(a patent application has been submitted for examination),and.I found that the high expression of OX40L molecule on the surface of DC was significantly higher than that of other antigen-presenting cells at steady states,and the adoptive transfer of the OX40L-expressing DCs could aggravate the severity of both acute and chronic vascular inflammation.However,if the OX40L-knockdown DCs are transferred,this phenomenon does not occur,suggesting that the surface molecule OX40L of DCs has a pro-inflammatory effect.Further investigation into the cellular mechanism of this effect revealed that the differentiation of CD4+but not CD8+regulatory T cells downstream of DCs was significantly affected(Chapter 4).Therefore,this project demonstrated the pro-inflammatory effect of DC surface costimulatory molecule OX40L on vascular inflammation,and revealed the immune mechanism via CD4+Treg.This study may provide a theoretical basis for the development of therapeutic drug targeting OX40L for the treatment of inflammatory vascular diseases.