RelB as a master regulator of the thymic medulla: characterization of factors that control RelB expression and the role of the RelB target gene Enpp2/Atx
Immunology
Final Report Abstract
The initial goal of this grant was to better understand the regulation of RelB, the master regulator of mTEC development. The data that were generated in the context of this proposal show that classical NF-κB signaling, which leads to the activation of RelA and c-Rel is as essential for mTEC development as the alternative pathway which activates RelB. Furthermore, the results showed that the role of RelA and c-Rel is to upregulate the transcription of RelB by directly binding to the Relb promoter. Analyses of appropriate reporter mice further demonstrated that both NF-κB activity and RelB expression are mainly confined to mature mTECs, corroborating the link between both events in these cells. Thus, these data reveal a crosstalk mechanism between classical and alternative NF-κB pathways that tightly controls the development of mature mTECs to ensure self-tolerance. Analysis of thymic endothelial and mesenchymal cells from RelBnull mice by FACS revealed no further essential role for RelB in the development of the thymic stroma.
Publications
- (2015) The deubiquitinating enzyme CYLD regulates the differentiation and maturation of thymic medullary epithelial cells. Immunol Cell Biol., 93, 558-566
Reissig, S., Hövelmeyer, N., Tang, Y., Weih, D., Nikolaev, A., Riemann, M., Weih, F., & Waisman, A.
(See online at https://doi.org/10.1038/icb.2014.122) - (2016) Classical and alternative NF-κB signaling cooperate in regulating adipocyte differentiation and function. Int J Obes., 40, 452-459
Weidemann, A., Lovas, A., Rauch, A., Andreas, N., von Maltzahn, J., Riemann, M., & Weih, F.
(See online at https://dx.doi.org/10.1038/ijo.2015.198) - (2017) Central immune tolerance depends on crosstalk between the classical and alternative NF-κB pathways in medullary thymic epithelial cells. J Autoimmun., 81, 56-67
Riemann, M., Andreas, N., Fedoseeva, M., Meier, E., Weih, D., Freytag, H., Schmidt-Ullrich, R., Klein, U., Wang, ZQ., & Weih, F.
(See online at https://doi.org/10.1016/j.jaut.2017.03.007) - (2017) RelB+ steady-state migratory dendritic cells control the peripheral pool of the natural Foxp3+ regulatory T cells. Front Immunol., 8, 726
Döhler, A., Schneider, T., Eckert, I., Ribechini, E., Andreas, N., Riemann, M., Reizis, B., Weih, F., & Lutz, M.B.
(See online at https://doi.org/10.3389/fimmu.2017.00726) - (2018) A new RelB-dependent CD117+ CD172a+ murine DC subset preferentially induces Th2 differentiation and supports airway hyperresponses in vivo. Eur J Immunol., 48, 923-936
Andreas, N., Riemann, M., Castro, C.N., Groth, M., Koliesnik, I., Engelmann, C., Sparwasser, T., Kamradt, T., Haenold, R., & Weih, F.
(See online at https://doi.org/10.1002/eji.201747332)
