Angeborene Immunität bei Rheumatologischen Erkrankungen

Macrophage biology and innate networks in chronic inflammatory diseases

Triantafyllopoulou_klein

Einleitung

My laboratory aims to understand macrophage biology and cross-talk with innate and epithelial cells in the context of chronic inflammation, with the ultimate goal to generate new treatment strategies. In the last years we have focused on the mechanisms of macrophage differentiation and function in chronic granulomatous and autoimmune pathologies.

Granulomatous diseases of non-infectious etiology include sarcoidosis, granulomatosis with polyangiitis, giant cell arteritis and granulomatous inflammatory bowel disease. Their common hallmark 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. Work in our lab has shown that granuloma-specific macrophage programs are instructed by a combination of growth, inflammatory and genotoxic stress signals (Herrtwich et al. Cell 2016). Current work aims to dissect the mechanisms of granuloma macrophage programming and the role of granuloma macrophages in disease evolution.

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. In previous work, we showed that macrophages activated by type I interferons are programed to promote epithelial cell proliferation and glomerulonephritis (Triantafyllopoulou et al. PNAS 2010). Current work is based on the concept that organ damage does not depend on the presence of autoantibodies alone but requires bypassing an inflammatory threshold. Our goal is to define the early cascade of events that determine target organ susceptibility to autoimmune organ damage.

Ausgewählte Publikationen

1: Horn V, Triantafyllopoulou A. DNA damage signaling and polyploid macrophages in chronic inflammation. Curr Opin Immunol. 2017 Dec 1;50:55-63. doi:10.1016/j.coi.2017.11.002. [Epub ahead of print] Review. PubMed PMID: 29202328.

2: 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. Cell. 2016 Nov 17;167(5):1264-1280.e18. doi:10.1016/j.cell.2016.09.054. Epub 2016 Oct 27. PubMed PMID: 28084216.

3: 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.

Mitarbeiter

Group Leader
Dr. Antigoni Triantafyllopoulou

Physician Scientists
Stylianos-Iasonas Biniaris-Georgallis
Dr. med. Tom Aschman

Medical Students
Zhen Zeng
Manuel Knoll

Technical Assistance
Frauke Schreiber

Kooperationspartner

Prof. Vassilis Gorgoulis (Athens)
Prof. Andreas Diefenbach (Berlin)
PD Dr. Anja Kühl (Berlin)
Prof. Anja Hauser (Berlin)
Prof. Andres Lopez-Contreras (Danemark)
Dr. Mario Zaiss (Erlangen)
Prof. Reinhard Voll (Freiburg)
Prof. Wolfgang Kühn (Freiburg)
Prof. Peter Staeheli (Freiburg)
Prof. Susanne Herold (Gießen)
Prof. Tobias Huber, PD Dr. Oliver Kretz (Hamburg)
Dr. Indrajit Nanda (Würzburg)

Dr. Antigoni Triantafyllopoulou

Group Leader, Laboratory Innate Immunity in Rheumatic Diseases
Fachärztin für Rheumatologie und klinische Immunologie

Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie
Charité - Universitätsmedizin Berlin

Deutsches Rheuma-Forschungszentrum Berlin (DRFZ)
Ein Institut der Leibniz-Gemeinschaft
Charitéplatz 1
10117 Berlin
Tel.
+49-30-28460-734 (office)
+49-30-28460-675 (lab)
Fax.
+49-30-28460-603

e-mail
Triantafyllopoulou@drfz.de
antigoni.triantafyllopoulou@charite.de

Keywords
Macrophages
Innate immunity
Chronic inflammation
Granulomatous diseases
Autoimmune organ damage
Rheumatic diseases

Radbruch Prof. Dr. rer. nat. Andreas Radbruch Zellbiologie Triantafyllopoulou_klein Dr. Antigoni Triantafyllopoulou Angeborene Immunität bei Rheumatologischen Erkrankungen Thurley Dr. Kevin Thurley Systembiologie der Entzündung Ahmed Hegazy Prof. Dr. med. Dr. rer. nat. Ahmed N. Hegazy Entzündungsmechanismen Polansky Dr. Julia Polansky-Biskup Immun-Epigenetik Melchers Prof. Dr. Fritz Melchers Lymphozytenentwicklung Farzin Mashreghi Dr. Mir-Farzin Mashreghi Therapeutische Genregulation Kruglov Dr. rer. nat. Andrey Kruglov Chronische Entzündung Loehning Prof. Dr. Max Löhning Pitzer-Labor Arthroseforschung Kubagawa Prof. Dr. Hiromi Kubagawa Humoral Immune Regulation Hauser Prof. Dr. med. vet. Anja Erika Hauser Immundynamik Tokoyoda Dr. Koji Tokoyoda Osteoimmunologie Scheffold Prof. Dr. rer. nat. Alexander Scheffold Zelluläre Immunologie Niesner Dr. rer. nat. Raluca Niesner Biophysikalische Analytik Strangfeld Dr. med. Anja Strangfeld Pharmakoepidemiologie Minden Prof. Dr. med. Kirsten Minden Kinder- und Jugendrheumatologie Listing Dr. Joachim Listing Biometrie / Klinische Studien Angela_Zink_230x230 Prof. Dr. Angela Zink Versorgungsforschung Worm Prof. Dr. med. Margitta Worm Allergologie Poddubnyy Prof. Dr. Denis Poddubnyy Spondyloarthritiden Riemekasten Prof. Dr. med. Gabriela Riemekasten Zell-Autoimmunität Hiepe Prof. Dr. med. Falk Hiepe Autoimmunologie Hamann Prof. Dr. rer. nat. Alf Hamann Experimentelle Rheumatologie Doerner Prof. Dr. med. Thomas Dörner B-Zell Gedächtnis Buttgereit Prof. Dr. med. Frank Buttgereit Glucokortikoide & Bioenergetik Romagnani Prof. Dr. Chiara Romagnani Angeborene Immunität Hutloff Dr. rer. nat. Andreas Hutloff Chronische Immunreaktionen Fillatreau Prof. Dr. rer. nat. Simon Fillatreau Immunregulation Baumgrass Prof. Dr. Ria Baumgrass Signaltransduktion Nedospasow Prof. Dr. Sergei Nedospasov Entzündungsbiologie