BMDC Inhibits The Proliferation Of Thymic Epithelial Cell Line MTEC1 Cells Through Jagged1/Notch3 Signal

Objective:To explore the manchnism of thymic degeneration and atrophy after who suffered from serious infectious and transplantation rejection.It may provide the theoretical basis and technical support for the therapy of thymic atrophy caused by these serious diseasesand the benefit ofreconstruction of the immunodeficiency of T cells.Method:The bone marrow dendritic cells?BMDC?,induced by GM-CSF and IL-4 from bone marrow hemopoietic stem cells of EGFP^Tg/+mice and activated by LPS,were injected into C57BL/6 mice via intracardiac injection.In the thymus,the proportion of GFP⁺CD11c⁺cells was determined by flow cytometry.The expression level of Jagged1on the surface of BMDC was detected by flow cytometry,while the expression levels of Notch1 and Notch3 in thymic epithelial cells were determined by immunofluorescence.Mouse thymic epithelial cell line 1?mTEC1?was co-cultured with BMDC or coated Jagged1 recombination protein in different concentrations and the cell proliferation was evaluated with a 5-ethynyl-2'-deoxyuridine?EdU?incorpra-tion assay.The?-secretase inhibitor?DAPT?was added to the both co-cultured sys-temtodetermine the proliferation of mTEC1.At last,the cell proliferation of mTEC1cells,infected with lentivirus expression vector of NICD3,was detected by EdU in-corpration assay.Results:The proportion of GFP⁺CD11c⁺cells was 1.7%in thymus,and it was evidencedthat activated BMDC could migrate into thymus.The expression level of Jagged1 in activated BMDC stimulated by LPS was higher than that of in inactivated BMDC.Notch1 mainly expressed in cortical thymic epithelial cells,while Notch3 rel-atively concentrated in medulla of thymus,and they were decreased with aging.The cell proliferation of mTEC1 could be inhibited while co-cultured directly with BMDC,and activated BMDC played a stronger role.Jagged1 downregulated the cell prolifer-ative of mTEC1 in a dose-dependent maner.The effect of cell proliferative inhibition in both co-cultured systems could be reversed by treating with DAPT.Finally,NICD3-infected mTEC1 showed obvious lower proliferative rate.Conclusion:The peripheral activated BMDC could migrate into thymus and in-hibit the cell proliferation of thymic epithelial cells via activated Jagged1/Notch3 sig-nal pathway.