University Medical Center Göttingen. Website
Institute for Cellular and Molecular Immunology. Humboldtallee 34, 37073 Göttingen, Germany
Mouse Models of Chronic Inflammation, T cell and Macrophage Function, Mechanisms of Glucocorticoids
Chronic inflammatory diseases are a highly prevalent group of pathogenic conditions that may affect any organ or tissue. Mostly, these disorders are treated with glucocorticoids (GC), steroid hormones that potently ameliorate clinical symptoms by inhibiting innate and acquired immune responses. They achieve many of their effects by modulating T cell and macrophage function but they impact many other cell types as well. Notwithstanding their unsurpassed therapeutic efficacy, some patients are resistant to GC while others experience side effects such as gastric ulcer or muscle wasting. Thus, efforts are warranted to improve our understanding of the mechanisms of GC and to develop new therapeutic concepts. Currently, our lab focuses on four major inflammatory diseases, namely multiple sclerosis, graft-versus-host disease, allergic asthma and colitis. We have established pre-clinical mouse models to study the immunological basis of these diseases and the mode of GC action in their treatment. Furthermore, new strategies to optimize GC delivery by use of inorganic-organic hybrid nanoparticles are currently under way. We hope to translate some of our concepts into the clinic soon and thereby make GC therapy more efficient and tolerable in the future.
- Theiss-Suennemann, J., Jörß, K., Messmann, J.J., Reichardt, S.D., Montes-Cobos, E., Lühder, F., Gröhne, H.J., Tuckermann, J.P., Wolff, H.A., Dressel, R., Strauß, G., and Reichardt, H.M. (2015). Glucocorticoids attenuate acute graft-versus-host disease by suppressing the cytotoxic capacity of CD8+ T cells. Journal of Pathology 235, 646-655.
- Wang, J., Wegener, J.E., Huang, T.-E., Sripathy, S., De Jesus-Cortes, H., Xu, P., Tran, S., Knobbe, W., Leko, V., Britt, J., Starwalt, R., McDaniel, L., Ward, C., Parra, D., Newcomb, B., Lao, U., Nourigat, C., Flowers, D.A., Cullen, S., Jorstad, N.L., Yang, Y., Glaskova, L., Vigneau, S., Kozlitina, J., Yetman, M.J., Jankowsky, J.L., Reichardt, S.D., Reichardt, H.M., Gärtner, J., Bartolomei, M.S., Fang, M., Loeb, K., Keene, C.D., Bernstein, I., Goodell, M., Brat, D.J., Huppke, P., Neul, J., Bedalov, A., Pieper, A.A. (2015). Wild type microglia do not arrest pathology in mouse models of Rett syndrome. Nature 521, E1-E4.
- Vettorazzi, S., Bode, C., Dejager, L., Frappart, L., Shelest, E., Klaßen, C., Tasdogan, A., Reichardt, H.M., Libert, C., Schneider, M., Weih, F., Uhlenhaut, N.H., David, J.-P., Gräler, M., Kleiman, A., and Tuckermann, J.P. (2015). Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1. Nature Communications 6, 7796.
- Montes-Cobos, E., Ring, S., Fischer, H.J., Heck, J., Strauß, J., Schwaninger, M., Reichardt, S.D., Feldmann, C., Lühder, F., and Reichardt, H.M. (2017). Targeted delivery of glucocorticoids to macrophages in a mouse model of multiple sclerosis using inorganic-organic hybrid nanoparticles. Journal of Controlled Release 245, 157-169.
- Klaßen, C., Karabinskaya, A., Dejager, L., Vettorazzi, S., Van Moorleghem, J., Lühder, F., Meijsing, S.H., Tuckermann, J.P., Bohnenberger, H., Libert, C., and Reichardt, H.M. (2017). Airway epithelial cells are crucial targets of glucocorticoids in a mouse model of allergic asthma. Journal of Immunology (doi: 10.4049/jimmunol.1601691).