Role of dendritic cell subsets in the induction of central (thymic) tolerance to oral antigens
Final Report Abstract
We are in the process of developing a system to track DC migration and systemic spread of orally fed antigen. By using conventional FACS and CyTOF of antigen surrogate uptake, we can recapitulate and extend published studies about oral antigen handling by DC. These processes are important for both peripheral and thymic Treg induction, which in turn play crucial roles to limit inflammatory processes. Our data indicate that and clarify why the thymus is critically involved in oral tolerance, a concept has failed to translate to clinical success. We can speculate that humans may thus lack the requirements to create central (thymic) Treg: thymic output rapidly declines during adolescence, and T cells pools are replenished through proliferation rather than thymic activity.
Publications
- Generation and transcriptional programming of intestinal dendritic cells: essential role of retinoic acid. Mucosal Immunol. 2016 Jan;9(1):183-93
Zeng R, Bscheider M, Lahl K, Lee M, Butcher EC
(See online at https://doi.org/10.1038/mi.2015.50) - Vitamin D immunoregulation through dendritic cells. Immunology. 2016 Jul;148(3):227-36
Bscheider M, Butcher EC
(See online at https://dx.doi.org/10.1111/imm.12610)
