Dendritic cells (DCs) are potent Antigen Presenting Cells capable of stimulating naive T-cells to develop effector function. DCs appear to decode inflammatory signals and use this information to orchestrate an immune response, and are therefore thought to have an essential role in regulating immunity. Because of this essential regulatory role, the manipulation of DC function is considered a promising avenue for the design of immunotherapies. However, the efficacy of clinical trials utilizing DC-based vaccines has been poor, suggesting that our understanding of DC function may be incomplete. This is in part be due to how rare DCs are and consequently difficult to isolate (especially from humans). As a result, in vitro experimental systems have been developed to study DCs. It is unclear, however, if the results from these in vitro systems, which have formed the basis for clinical trials of DC-based therapeutics, actually apply to DCs in vivo. Our preliminary results show that while inflammatory stimuli in vitro causes certain changes in mouse DCs (which has been known for over 10 years), inflammatory stimuli delivered to DCs in vivo does not have identical effects, suggesting that there may indeed be important differences between DCs in vitro and in vivo. To this end, we propose to analyze the antigen capture, processing, and presentation by mouse DCs in situ, and to examine how these essential functions are regulated by inflammatory signals in vivo. We expect this project to provide new information on how DCs may be manipulated for the purpose developing more effective immunotherapies.
A variety of diseases affecting the aging population involve immune dysfunction. These include the inability to clear infections due to the lack of an effective immune response, autoimmune disease when the immune system is activated to destroy healthy tissues, and perhaps even cancer as the immune system fails to recognize and destroy the aberrant altered cells of a tumor. By studying the cells that regulate immune responses, we will find new ways to take control of the immune system and treat these diseases.
| Drutman, Scott B; Kendall, Julia C; Trombetta, E Sergio (2012) Inflammatory spleen monocytes can upregulate CD11c expression without converting into dendritic cells. J Immunol 188:3603-10 |
| Drutman, Scott B; Trombetta, E Sergio (2010) Dendritic cells continue to capture and present antigens after maturation in vivo. J Immunol 185:2140-6 |
