RelB als ein Hauptregulator der Thymusmedulla: Charakterisierung von Faktoren, welche die RelB Expression steuern und die Bedeutung des RelB Zielgens Enpp2/Atx

• Antragsteller: Professor Dr. Christoph Englert, seit 11/2014
• Fachliche Zuordnung: Zellbiologie ; Immunologie
• Förderung: Förderung von 2009 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 154810081

• Erstellungsjahr: 2018

Zusammenfassung der Projektergebnisse

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.

Projektbezogene Publikationen (Auswahl)

• (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.
  (Siehe online unter 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.
  (Siehe online unter 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.
  (Siehe online unter 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.
  (Siehe online unter 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.
  (Siehe online unter https://doi.org/10.1002/eji.201747332)