Analysis 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
The focus of this project is on the role of APCs in experimental autoimmune encephalomyelitis (EAE), a mouse model for the human autoimmune disease of the central nervous system (CNS) multiple sclerosis (MS). In EAE, dendritic cells (DCs) play an important role as they present a self-antigen to naive T cells and thereby prime them. The primed CD4+ T cells migrate to the CNS where they cross the blood brain barrier (BBB) and cause a demyelination of neurons and a disturbance of oligodendrocytes. In order to cross the BBB, the T cells must be reactivated. It is currently unknown which kind of APCs are involved in this process. A specific cell population we are interested in are the endothelial cells of the blood brain barrier (BBB). It was shown before that these cells are capable of expressing MHCII and therefore could play a role in the reactivation of T cells.
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 mouse system called “LIPSTIC” which can be used to label immune cell interactions. It was generated at the Rockefeller University In New York City and it will allow us to label and analyze in an unbiased manner all APCs in the CNS that are involved in the interaction with CD4+ T cells. It is based on the interaction between CD40, expressed by APCs, and CD40-ligand, expressed by T cells. When two cells interact with each other, a substrate is transferred from the T cell to the APCs which labels them and allows for visualization using flow cytometry.4,5
The proposed project will make use of sophisticated mouse genetic systems, single cell sequencing and high dimensional flow cytometry as well as multiple 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
Nakandakari-Higa S, Canesso MCC, Walker S, Chudnovskiy A, Jacobsen JT, Bilanovic J, Parigi SM, Fiedorczuk K, Fuchs E, Bilate AM, Pasqual G, Mucida D, Pritykin Y, Victora GD. (2023) Universal recording of cell-cell contacts in vivo for interaction-based transcriptomics. bioRxiv [Preprint]. 2023 Apr 18:2023.03.16.533003. doi: 10.1101/2023.03.16.533003. Link