Projects Offered
Dorothee Dormann Edward Lemke Stamatis Papathanasiou Johannes Mayer_Ageing Johannes Mayer_Dynamics Daniel Sasca Natalia Soshnikova Tim Sparwasser Ari WaismanAnalysis of antigen-presenting cells interaction with T cells across the body during central nervous system autoimmunity
1-2 PhD projects offered in the IPP summer call Molecular Biomedicine & Ageing
Scientific Background
Dendritic cells (DCs) are myeloid cells that are important in the activation of T cells in immune responses 1. We found previously that mice made genetically to express a self-antigen by DCs are resistant to the development of experimental autoimmune encephalomyelitis (EAE), a mouse model for the human central nervous system (CNS) autoimmune disease multiple sclerosis. We found that when the DCs express the self-antigen in a noninflammatory condition, they lead to the generation of Treg cells which subsequently control the disease and lead to tolerance 2, 3.
DCs activate T cells in the lymph nodes, but their role as antigen presenting cells (APCs) in other organs, is less clear. In addition, it is not clear if in addition to DCs also play a role in the activation or modulation of T cells. One specific population we are interested in, are the endothelial cells of the blood brain barrier (BBB). Evidence indicate that these cells have the capacity to express MHC class II and thus to activate CD4+ T cells but this was never shown in a clear manner.
PhD project: Analysis of antigen-presenting cells interaction with T cells across the body during central nervous system autoimmunity
In the frame of this project, we will use a novel system, the so called LIPSTIC-system was generated at The Rockefeller University in New York that will allow us to label and analyze in an unbiased manner all antigen presenting cells in the body4. The proposed project will make use of sophisticated mouse genetic systems, single cell sequencing and high dimensional flow cytometry as well as many other cellular and molecular methods used in the lab.
If you are interested in this project, please select Waisman your group preference in the IPP application platform.
Publications relevant to the project
Waisman A, Lukas D, Clausen BE and Yogev N. (2017) Dendritic cells as gatekeepers of tolerance. Semin Immunopathol. 2017;39:153-163. Link
Yogev N, Frommer F, Lukas D, Kautz-Neu K, Karram K, Ielo D, von Stebut E, Probst HC, van den Broek M, Riethmacher D, Birnberg T, Blank T, Reizis B, Korn T, Wiendl H, Jung S, Prinz M, Kurschus FC and Waisman A. (2012) Dendritic Cells Ameliorate Autoimmunity in the CNS by Controlling the Homeostasis of PD-1 Receptor(+) Regulatory T Cells. Immunity. 2012;37:264-75. Link
Krienke C, Kolb L, Diken E, Streuber M, Kirchhoff S, Bukur T, Akilli-Ozturk O, Kranz LM, Berger H, Petschenka J, Diken M, Kreiter S, Yogev N, Waisman A, Kariko K, Tureci O and Sahin U. (2021) A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science. 2021;371:145-153. Link
Pasqual G, Chudnovskiy A, Tas JMJ, Agudelo M, Schweitzer LD, Cui A, Hacohen N and Victora GD. (2018) Monitoring T cell-dendritic cell interactions in vivo by intercellular enzymatic labelling. Nature. 2018;553:496-500. Link