Sorting of self and non-self as regulatory mechanism during the maintenance of self tolerance
Live Webinar 13 July 2016 6:00pm – 7:00pm
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- 25 min science presentation
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- 25 min Q&A
About the Speaker:
Gerhard Krönke is a newly appointed Professor of Translational Immunology at the University of Erlangen-Nuremberg and knows how to successfully combine clinical duties and research!
Gerhard studied Medicine in Vienna and completed his studies in 2002. Thereafter, he started to work as a post-doc in the Institute of Vascular Biology at the Medical University of Vienna and subsequently did a two-year post-doc at the University of Virginia. After his post-doc experiences he moved to Erlangen, Germany to start his residency at the Institute for Rheumatology and Clinical Immunology at the University’s Medical Clinic 3. In 2009, he started his own research group focusing on immunobiology and molecular mechanisms of inflammation. Since then, he has published his work in renowned scientific journals and recently, also has obtained one of the prestigious ERC Starting Grants in 2014. Since 2012, he also furthered his clinical career and has been appointed as an attending at the Institute for Rheumatology and Clinical Immunology. His outstanding ability to combine clinical duties and research projects has now led to an appointment as Professor for Translational Immunology at the University of Erlangen-Nuremberg.
During inflammation and infection, we are simultaneously confronted with both self and non-self in form of dying cells and microbes, respectively. Mechanisms that facilitate the non-immunogenic clearance of self-antigens derived from apoptotic and necrotic cells and that, in parallel, allow the initiation of an immune response against invading pathogens are incompletely understood.
Recent data from our laboratory show that the immune system actively sorts apoptotic cells (ACs) and bacteria into distinct subspecies of macrophages and dendritic cells thereby enabling a segregated processing of self and non-self as well as a differential immune response against these two entities. Incorrect sorting and aberrant uptake of AC-derived self-antigens by pro-inflammatory and antigen-presenting dendritic cells, however, results in the break of self-tolerance and autoimmunity.
Due to technical limitations, the identification and fate-mapping of specific phagocyte subsets that mediate the simultaneous clearance of dying cells and pathogens in vivo has remained largely elusive. We thus plan to develop novel tools that are based on cutting-edge technologies to comprehensively elucidate the sorting of dying cells and pathogens under inflammatory conditions in vivo. We plan to generate TAT-Cre transgenic mice and bacteria that will be used in conjunction with R26-eYFP reporter animals to permanently track phagocytes after ingestion of endogenously accumulated dying cells and pathogens, respectively. These approaches will enable us to characterize the involved phagocytes, study molecular mechanisms underlying the differential processing of self and non-self and follow the phagocyte’s migratory behaviour and its subsequent differentiation. The obtained data will not only provide insights into the pathogenesis of autoimmune and infectious diseases, but will also foster the development of novel therapeutic strategies for the treatment of such disorders.
Top 5 publications:
- Luo Y, Chen GL, Hannemann N, Ipseiz N, Krönke G, Bäuerle T, Munos L, Wirtz S, Schett G, Bozec A. Microbiota from Obese Mice Regulate Hematopoietic Stem Cell Differentiation by Altering the Bone Niche. Cell Metab. 2015;22:886-94.
- Rothe T, Gruber F, Uderhardt S, Ipseiz N, Rössner S, Oskolkova O, Blüml S, Leitinger N, Bicker W, Bochkov VN, Yamamoto M, Steinkasserer A, Schett G, Zinser E, Krönke G. 12/15-Lipoxygenase-mediated enzymatic lipid oxidation regulates DC maturation and function. J Clin Invest. 2015;125:1944-54.
- Harre U, Lang SC, Pfeifle R, Rombouts Y, Frühbeißer S, Amara K, Bang H, Lux A, Koeleman CA, Baum W, Dietel K, Gröhn F, Malmström V, Klareskog L, Krönke G, Kocijan R, Nimmerjahn F, Toes RE, Herrmann M, Scherer HU, Schett G. Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss. Nat Commun. 2015;6:6651.
- Palumbo-Zerr K, Zerr P, Distler A, Fliehr J, Mancuso R, Huang J, Mielenz D, Tomcik M, Fürnrohr BG, Scholtysek C, Dees C, Beyer C, Krönke G, Metzger D, Distler O, Schett G, Distler JH. Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis. Nat Med. 2015;21:150-8.
- Scholtysek C, Katzenbeisser J, Fu H, Uderhardt S, Ipseiz N, Stoll C, Zaiss MM, Stock M, Donhauser L, Böhm C, Kleyer A, Hess A, Engelke K, David JP, Djouad F, Tuckermann JP, Desvergne B, Schett G, Krönke G. PPARβ/δ governs Wnt signaling and bone turnover. Nat Med. 2013;19:608-13.