Macrophage biology and innate networks in chronic inflammatory diseases
Macrophage biology and innate cellular networks in chronic inflammatory diseases
Our group aims to understand innate immune biology in chronic diseases with the ultimate goal to unravel the spectrum of mechanisms leading to organ damage, and thus lay the ground for personalized medicine. In the last years, we have focused on the mechanisms of macrophage differentiation and function in chronic granulomatous and autoimmune pathologies.
Prominent examples of granulomatous diseases are infectious diseases such as tuberculosis, but also several inflammatory diseases, with unknown infectious triggers, including sarcoidosis, inflammatory bowel disease, rheumatoid arthritis and giant cell arteritis. The common hallmark of granulomatous diseases is the presence of granulomas, structures of organized inflammation that form in response to a persistent stimulus and replace healthy tissue. In granulomas, macrophage precursors acquire epithelial and polyploid programs. We showed that the DNA Damage Response, a fundamental cellular process activated in response to genotoxic stress, is not only significant for cancer development, but also instructs macrophage programs in chronic granulomatous diseases (Herrtwich et al. Cell 2016; reviewed in Horn et al, Curr Opin Immunol 2018). Current work aims to dissect the mechanisms of granuloma macrophage programming and the role of granulomas in disease progression.
A large number of autoimmune pathologies arise in the context of loss of tolerance against self-nucleic acids. This induces a chronic type I interferon response. We have shown that macrophages activated by type I interferons are programmed to promote epithelial cell proliferation and glomerulonephritis (Triantafyllopoulou et al. PNAS 2010). Current work aims to dissect the innate immune cell network that determines target organ susceptibility to autoimmune organ damage.
Autoimmune organ damage
Prof. Antigoni Triantafyllopoulou. MD
Stylianos-Iasonas Biniaris-Georgallis (Physician Scientist)
Anna Taranko, M.Sc.
Ana Kasapi, M.Sc.
Tejal Karmalkar, M.Sc.
Vajiheh Jafari, M.Sc.
- Prof. Dr. Vassilis Gorgoulis (Athens)
- Prof. Dr. Andreas Diefenbach (Berlin)
- PD Dr. Anja Kühl (Berlin)
- Prof. Dr. Anja Hauser (Berlin)
- Prof. Dr. Susanne Herold (Gießen)
- Dr. Christoph Hölscher (Börstel)
- Prof. Dr. Tobias Huber/PD Dr. Oliver Kretz (Hamburg)
- Dr. Masatoshi Kanda/Prof. Dr. Norbert Hübner (Berlin)
- Dr. Andrey Kruglov (Berlin)
- Prof. Dr. Wolfgang Kühn (Freiburg)
- Dr. Mir-Farzin Mashreghi (Berlin)
- Dr. Indrajit Nanda (Würzburg)
- Prof. Dr. Andres Lopez-Contreras (Danemark)
- Dr. Teodora Nikolova (Mainz)
- Dr. Kevin Thurley (Berlin)
- Prof. Dr. Reinhard Voll (Freiburg)
- Prof. Dr. Mario Zaiss (Erlangen)
- Gronke K, Hernández PP, Zimmermann J, Klose CSN, Kofoed-Branzk M, Guendel F, Witkowski M, Tizian C, Amann L, Schumacher F, Glatt H, Triantafyllopoulou A,Diefenbach A. Interleukin-22 protects intestinal stem cells against genotoxic stress. Nature. 2019 Feb;566(7743):249-253. doi: 10.1038/s41586-019-0899-7. Epub 2019 Jan 30.
- Horn V, Triantafyllopoulou A. DNA damage signaling and polyploid macrophages in chronic inflammation. Curr Opin Immunol. 2018 Feb;50:55-63.
- Herrtwich L, Nanda I, Evangelou K, Nikolova T, Horn V, Sagar, Erny D, Stefanowski J, Rogell L, Klein C, Gharun K, Follo M, Seidl M, Kremer B, Münke N, Senges J, Fliegauf M, Aschman T, Pfeifer D, Sarrazin S, Sieweke MH, Wagner D,Dierks C, Haaf T, Ness T, Zaiss MM, Voll RE, Deshmukh SD, Prinz M, Goldmann T,Hölscher C, Hauser AE, Lopez-Contreras AJ, Grün D, Gorgoulis V, Diefenbach A,Henneke P, Triantafyllopoulou A. DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas. 2016 Nov 17;167(5):1264-1280.e18. doi:10.1016/j.cell.2016.09.054. Epub 2016 Oct 27. PubMed PMID: 28084216.
- Triantafyllopoulou A, Franzke CW, Seshan SV, Perino G, Kalliolias GD, Ramanujam M, van Rooijen N, Davidson A, Ivashkiv LB. Proliferative lesions and metalloproteinase activity in murine lupus nephritis mediated by type I interferons and macrophages. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3012-7.doi: 10.1073/pnas.0914902107. Epub 2010 Jan 26. PubMed PMID: 20133703; PubMed Central PMCID: PMC2840310.