Study On The Role Of 4-1BB And CD40 Signals In Regulation Of TLR4 Expression

Toll like receptors (TLRs), the most important part in innate immunity, not only play a vital role in infectious diseases, but also have roles in immune responses to tumor and its sneaking. TLR4 has been intensively reported to participate in tumor immunity. Dendritic cells(DCs), as a primary promoter for immune responses, play an important role in many diseases, especially in tumor immunity. There have been many reports on the regulation of TLR4 by factors on monocytes and dendritic cells, but no reports about the regulation by the co-stimulator CD40 or 4-1BB.Therefor, this study was to investigate the expression of TLR4 after activating CD40 or 4-1BB on dendritic cell and monocytes.1. 4-1BB signal mediate the regulation of TLR4 expression on mouse dendritic cellsObjective: To study the regulatory effects of agonist 4-1BB (CD137) monoclonal antibody 2A on TLR4 expression in murine bone marrow derived dendritic cells (imDC) and in a murine DC cell line DC2.4. Methods: Flow cytometry was used to investigate the TLR4 expression on DCs under these conditions: different doses of 2A, LPS, 2A combined with LPS or addition of 2A after pre-stimulation of DCs by LPS. Results: LPS could down-regulate TLR4 expression on DCs, and the down-regulatory effect of LPS was maintained for 24 hours. On the contrary, 2A could up-regulate TLR4 expression on DCs, and this effect of 2A was maintained for 12 hours. Moreover, 2A could inhibit the down-regulatory effect of LPS on TLR4 expression. When DCs were stimulated by 2A after LPS pre-stimulation, 2A could still up-regulate TLR4 expression on DCs. We obtained the similar results both on BMDC and DC2.4 cell line. Conclusion: 4-1BB signal could up-regulate the expression of TLR4 on dendritic cell.2. The study on the role of CD40 signal in regulation of TLR4 expression on human...