We used conditional ablation of STAT1 in macrophages, monocytes and granulocytes of mice and showed that myeloid STAT1 protects from early murine cytomegalovirus replication and pathology in spleen. Unexpectedly, we found that myeloid STAT1 drives extramedullary haematopoiesis (EMH). STAT1 promotes EMH not only after virus infection but also upon sterile inflammation induced by CpG oligodeoxynucleotides. Using additional genetically engineered mice we analysed the impact of upstream signals known to activate STAT1 and observed that virus-induced EMH does not rely on type I or type II IFN signaling in myeloid cells or IL-27 signaling in all cell types. Our studies provide the first genetic evidence that STAT1-dependent signaling in myeloid cells restricts MCMV at early time points post infection and induces compensatory (stress-induced) haematopoiesis in the spleen.

Publication in Cell Reports

Riem Gawish*, Tanja Bulat*, Mario Biaggio*, Caroline Lassnig, Zsuzsanna Bago-Horvath, Sabine Macho-Maschler, Andrea Poelzl, Natalija Simonović, Michaela Prchal-Murphy, Rita Rom, Lena Amenitsch, Luca Ferrarese, Juliana Kornhoff, Therese Lederer, Jasmin Svinka, Robert Eferl, Markus Bosmann, Ulrich Kalinke, Dagmar Stoiber, Veronika Sexl, Astrid Krmpotić, Stipan Jonjić, Mathias Müller, and Birgit Strobl

*equal author contribution

Myeloid Cells Restrict MCMV and Drive Stress-Induced Extramedullary Hematopoiesis through STAT1 (2019); Doi: https://doi.org/10.1016/j.celrep.2019.02.017

We used conditional ablation of TYK2 in mice and showed that TYK2 promotes NK cell activity in tumour surveillance and the defence against Listeria monocytogenes infection through cell-extrinsic and -intrinsic mechanisms. The key discoveries are as follows: NK cell-extrinsic TYK2 drives peripheral NK cell maturation, demethylation of the Ifng locus, activating receptor-induced IFNg production, cytotoxicity and anti-tumour activity; the NK cell defects observed in Tyk2-/- mice can be restored by recombinant IL-15/IL-15Rα treatment; NK cell-intrinsic TYK2 signalling mediates infection-induced IFNg production and acts protective during Listeria monocytogenes infection.

Collectively, our study disclosed TYK2 functions that remained unrecognized in mice with complete TYK2 deficiency. Our findings that cytotoxic defects of Tyk2-/- NK cells can be rescued by IL-15/IL-15Rα treatment suggest that unwanted effects of TYK2 inhibitors in tumour therapy may be overcome by boosting NK cell activity.

Publication in Journal of Immunology

Natalija Simonović * , Agnieszka Witalisz-Siepracka *, Katrin Meissl, Caroline Lassnig, Ursula Reichart,  Thomas Kolbe,  Matthias Farlik, Christoph Bock, Veronika Sexl, Mathias Müller, and Birgit Strobl

*equal author contribution

NK Cells Require Cell-Extrinsic and -Intrinsic TYK2 for Full Functionality in Tumor Surveillance and Antibacterial Immunity (2019); Doi:

https://doi.org/10.4049/jimmunol.1701649

The symposium will be held at the Vetmeduni Vienna on January 31 and February 01, 2019. The symposium invited speakers from the Vienna Life Science community and from the Vetmeduni Vienna who work in basic and translational biomedical sciences to pave the road for new therapeutic concepts. Their research contributions serve as role models for students and early career scientists. We train students of the MSc program ‘Comparative Biomedicine’on our campus under the principle of “One Health – One Medicine”. The symposium is organized and supported by SFB F61 JakStat Monarchies.

Link to PDF of Program

An international research team led by Veronika Sexl from Vetmeduni Vienna and supported by other members of SFB ‚JakStat Monarchies‘ have made an important discovery that could lead to a better understanding of lymphocytic leukemia: the STAT5B protein – but not the highly related STAT5A isoform – is crucial for disease development by suppressing interferon signals during leukemic transformation. Our findings will enable novel therapeutic approaches in precision medicine.

Publication in Leukemia:

Sebastian Kollmann, Eva Grundschober, Barbara Maurer, Wolfgang Warsch, Reinhard Grausenburger, Leo Edlinger, Jani Huuhtanen, Sabine Lagger, Lothar Hennighausen, Peter Valent, Thomas Decker, Birgit Strobl, Mathias Mueller, Satu Mustjoki, Andrea Hoelbl-Kovacic and Veronika Sexl

Twins with different personalities: STAT5B—but not STAT5A—has a key role in BCR/ABL-induced leukemia (2019), https://doi.org/10.1038/s41375-018-0369-5

Facial tumours of Tasmanian devils belong to rare cases of transmissible cancers. More than 90% of the population of devils is extinct due to two distinct Schwannoma cell lines that spread among the species. They are of great interest for biomedical research, as they allow the study of fundamental properties of cancer cells and how they escape the host´s immune system. Using cutting-edge technologies, scientists of the group of Andreas Bergthaler at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and members of the groups of Richard Moriggl and Christoph Bock, both SFB JakStat Monarchies at the Vienna University of Veterinary Medicine together with international collaborators identified the ERBB receptor-STAT3 axis as key molecular mechanisms allowing for the transmissibility of the tumour cells. Importantly, the consortium showed that the inhibition of ERBB receptors with a selective tyrosine kinase inhibitor or pharmacologic intervention of STAT3 could selectively kill the transmissible cancer cells upregulating MHC class I allowing for immune cell recognition. This could play an important role for the treatment and understanding of the disease to rescue the Tasmanian devil in the isolated island from extinction.

Publication in Cancer Cell:

Lindsay Kosack, Bettina Wingelhofer, Alexandra Popa, Anna Orlova, Benedikt Agerer, Bojan Vilagos, Peter Majek, Katja Parapatics, Alexander Lercher, Anna Ringler, Johanna Klughammer, Mark Smyth, Kseniya Khamina, Hatoon Baazim, Elvin D. de Araujo, David A. Rosa, Jisung Park, Gary Tin, Siawash Ahmar, Patrick T. Gunning, Christoph Bock, Hannah V. Siddle, Gregory M. Woods, Stefan Kubicek, Elisabeth P. Murchison, Keiryn L. Bennett, Richard Moriggl and Andreas Bergthaler

The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease (2019) DOI:https://doi.org/10.1016/j.ccell.2018.11.018

See also “The Deadly Bite of STAT3” mini review Cancer Cell by Hagen Schwenzer and Ariberto Fassati: DOI:https://doi.org/10.1016/j.ccell.2018.12.004