Our group is interested in studying the molecular mechanisms determining local regulation of immune responses in tissues, in particular in the liver. We employ modern cutting edge technologies to characterize the interaction of immune cells with tissue cells and how this shapes the quality of immune responses in the context of pathogen infection, metabolic challenges and chronic inflammation leading to tumor development. Understanding the principles of local regulation of immune responses is key to understand the molecular pathophysiology of organ-specific diseases. Such knowledge forms the basis for developing next-generation immune therapies based on novel concepts for therapeutic vaccination and for improving immune diagnostics through quantitative measurement of immune responses in tissues.
We are focusing on the regulation of immune responses in the liver and how the mechanistic understanding of the local balance between immunogenic and tolerogenic signals can be employed to achieve clearance of chronic viral infections and to eradicate tumor cells from the liver. We are further exploring the role of the liver in systemic immunity and how T cells primed in the liver contribute to protective immunity against pathogen infection.
We invite you to explore our homepage for further information.
Thomson AW, Knolle PA. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol 2010, 10(11): 753-766.
Protzer U, Maini MK, Knolle PA. Living in the liver: hepatic infections. Nat Rev Immunol 2012, 12(3): 201-213.
Wohlleber D, Kashkar H, Gartner K, Frings MK, Odenthal M, Hegenbarth S, Limmer A, Cederbrant K, Heikenwalder M, Pasparakis M, Protzer U, Dienes HP, Kurts C, Kronke M, Knolle PA. TNF-Induced Target Cell Killing by CTL Activated through Cross-Presentation. Cell Reports 2012, 2(3): 478-487.
Huang LR, Wohlleber D, Reisinger F, Jenne CN, Cheng RL, Abdullah Z, Schildberg FA, Odenthal M, Dienes HP, van Rooijen N, Schmitt E, Garbi N, Croft M, Kurts C, Kubes P, Protzer U, Heikenwalder M, Knolle PA. Intrahepatic myeloid-cell aggregates enable local proliferation of CD8(+) T cells and successful immunotherapy against chronic viral liver infection. Nat Immunol 2013, 14(6): 574-583.
Böttcher JP, Schanz O, Wohlleber D, Abdullah Z, Debey-Pascher S, Staratschek-Jox A, Hochst B, Hegenbarth S, Grell J, Limmer A, Atreya I, Neurath MF, Busch DH, Schmitt E, van Endert P, Kolanus W, Kurts C, Schultze JL, Diehl L, Knolle PA. Liver-Primed Memory T Cells Generated under Noninflammatory Conditions Provide Anti-infectious Immunity. Cell Reports 2013, 3(3): 779-795.
Böttcher JP, Schanz O, Garbers C, Zaremba A, Hegenbarth S, Kurts C, Beyer M, Schultze JL, Kastenmuller W, Rose-John S, Knolle PA. IL-6 trans-Signaling-Dependent Rapid Development of Cytotoxic CD8(+) T Cell Function. Cell Reports 2014, 8(5): 1318-1327.
Wolf MJ, Adili A, Piotrowitz K, Abdullah Z, Unger K, Karin M, Kopf M, Knolle P, Weber A, Heikenwalder M. Metabolic Activation of Intrahepatic CD8(+) T Cells and NKT Cells Causes Nonalcoholic Steatohepatitis and Liver Cancer via Cross-Talk with Hepatocytes. Cancer Cell 2014, 26(4): 549-564.