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Decisions in metabolic inflammation of the liver: Adhesive interactions involved in leukocyte retention and resolution of inflammation in metabolic-inflammatory liver disease

Total Cost €


EC-Contrib. €






Project "DEMETINL" data sheet

The following table provides information about the project.


Organization address
postcode: 1069

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 1˙953˙250 €
 EC max contribution 1˙953˙250 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-01-01   to  2021-12-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

Resolution of acute inflammation, involving limiting further leukocyte recruitment, apoptosis and clearance of inflammatory cells via macrophages as well as egress of the inflammatory cells, is operative in acute inflammation but dysfunctional in chronic inflammatory disease. In the latter scenario, the retention and activation of leukocytes in the inflamed tissue linked with failure to resolve inflammation contributes to perpetuation of organ damage and loss of homeostasis. Interestingly, persistent inflammation in insulintarget organs, such as the adipose tissue and the liver in the context of obesity significantly contributes to development of insulin resistance (IR), diabetes and non-alcoholic fatty liver disease (NAFLD). So far, investigations have mainly addressed obesity-related inflammatory mechanisms in the AT and rather less in other metabolic organs, e.g. the liver. Therefore, the aims of this proposal are: (i) To characterize in the context of obesity-related metabolic disease novel processes mediating inflammatory cell retention, especially in the liver. In this context, we will also address the novel hypothesis that adhesive interactions of inflammatory cells (with e.g. parenchymal cells) in the metabolically challenged environment of obese organs may activate them via alterations in their cellular metabolism, thereby contributing to perpetuation of inflammation. (ii) To understand resolution of inflammation including inflammatory cell egress from metabolic organs, especially from the liver in metabolic-inflammatory disease. To this end, we will also utilize models of acute inflammation, which is capable to resolve, in order to understand resolution principles and apply them to non-resolving metabolic-inflammatory disease. In this regard, we will also assess the therapeutic potential of novel inflammation-modulating factors identified by our lab.


year authors and title journal last update
List of publications.
2019 Triantafyllos Chavakis, Ioannis Mitroulis, George Hajishengallis
Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation
published pages: 802-811, ISSN: 1529-2908, DOI: 10.1038/s41590-019-0402-5
Nature Immunology 20/7 2020-02-13
2019 Ioannis Kourtzelis, Xiaofei Li, Ioannis Mitroulis, Daniel Grosser, Tetsuhiro Kajikawa, Baomei Wang, Michal Grzybek, Janusz von Renesse, Aleksander Czogalla, Maria Troullinaki, Anaisa Ferreira, Christian Doreth, Klara Ruppova, Lan-Sun Chen, Kavita Hosur, Jong-Hyung Lim, Kyoung-Jin Chung, Sylvia Grossklaus, Anne Kathrin Tausche, Leo A. B. Joosten, Niki M. Moutsopoulos, Ben Wielockx, Antonio Castrill
DEL-1 promotes macrophage efferocytosis and clearance of inflammation
published pages: 40-49, ISSN: 1529-2908, DOI: 10.1038/s41590-018-0249-1
Nature Immunology 20/1 2019-08-29
2017 Kyoung-Jin Chung, Antonios Chatzigeorgiou, Matina Economopoulou, Ruben Garcia-Martin, Vasileia I Alexaki, Ioannis Mitroulis, Marina Nati, Janine Gebler, Tjalf Ziemssen, Susan E Goelz, Julia Phieler, Jong-Hyung Lim, Katia P Karalis, Thalia Papayannopoulou, Matthias Blüher, George Hajishengallis, Triantafyllos Chavakis
A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity
published pages: 654-664, ISSN: 1529-2908, DOI: 10.1038/ni.3728
Nature Immunology 18/6 2019-06-18
2018 Rashim Pal Singh, Tatyana Grinenko, Beáta Ramasz, Kristin Franke, Mathias Lesche, Andreas Dahl, Max Gassmann, Triantafyllos Chavakis, Ian Henry, Ben Wielockx
Hematopoietic Stem Cells but Not Multipotent Progenitors Drive Erythropoiesis during Chronic Erythroid Stress in EPO Transgenic Mice
published pages: 1908-1919, ISSN: 2213-6711, DOI: 10.1016/j.stemcr.2018.04.012
Stem Cell Reports 10/6 2019-06-18
2017 Marta Prucnal, Bettina Gercken, Matina Economopoulou, George Hajishengallis, Triantafyllos Chavakis, Pallavi Subramanian
Endothelial cell-specific overexpression of developmental endothelial locus-1 does not influence atherosclerosis development in ApoE-/- mice
published pages: 2003-2005, ISSN: 0340-6245, DOI: 10.1160/th17-03-0160
Thrombosis and Haemostasis 117/10 2019-06-18
2018 Ioannis Mitroulis, Klara Ruppova, Baomei Wang, Lan-Sun Chen, Michal Grzybek, Tatyana Grinenko, Anne Eugster, Maria Troullinaki, Alessandra Palladini, Ioannis Kourtzelis, Antonios Chatzigeorgiou, Andreas Schlitzer, Marc Beyer, Leo A.B. Joosten, Berend Isermann, Mathias Lesche, Andreas Petzold, Kai Simons, Ian Henry, Andreas Dahl, Joachim L. Schultze, Ben Wielockx, Nicola Zamboni, Peter Mirtschink, Ãœnal Coskun, George Hajishengallis, Mihai G. Netea, Triantafyllos Chavakis
Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity
published pages: 147-161.e12, ISSN: 0092-8674, DOI: 10.1016/j.cell.2017.11.034
Cell 172/1-2 2019-06-18
2018 Andreea-Manuela Mirea, Cees J. Tack, Triantafyllos Chavakis, Leo A.B. Joosten, Erik J.M. Toonen
IL-1 Family Cytokine Pathways Underlying NAFLD: Towards New Treatment Strategies
published pages: 458-471, ISSN: 1471-4914, DOI: 10.1016/j.molmed.2018.03.005
Trends in Molecular Medicine 24/5 2019-06-18
2017 Thati Madhusudhan, Hongjie Wang, Sanchita Ghosh, Wei Dong, Varun Kumar, Moh\'d Mohanad Al-Dabet, Jayakumar Manoharan, Sumra Nazir, Ahmed Elwakiel, Fabian Bock, Shrey Kohli, Andi Marquardt, Ibrahim Sögüt, Khurrum Shahzad, Andreas J. Müller, Charles T. Esmon, Peter P. Nawroth, Jochen Reiser, Triantafyllos Chavakis, Wolfram Ruf, Berend Isermann
Signal integration at the PI3K-p85-XBP1 hub endows coagulation protease activated protein C with insulin-like function
published pages: 1445-1455, ISSN: 0006-4971, DOI: 10.1182/blood-2017-02-767921
Blood 130/12 2019-06-18
2018 Tatyana Grinenko, Anne Eugster, Lars Thielecke, Beáta Ramasz, Anja Krüger, Sevina Dietz, Ingmar Glauche, Alexander Gerbaulet, Malte von Bonin, Onur Basak, Hans Clevers, Triantafyllos Chavakis, Ben Wielockx
Hematopoietic stem cells can differentiate into restricted myeloid progenitors before cell division in mice
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-04188-7
Nature Communications 9/1 2019-06-18
2017 Ioannis Mitroulis, Lan-Sun Chen, Rashim Pal Singh, Ioannis Kourtzelis, Matina Economopoulou, Tetsuhiro Kajikawa, Maria Troullinaki, Athanasios Ziogas, Klara Ruppova, Kavita Hosur, Tomoki Maekawa, Baomei Wang, Pallavi Subramanian, Torsten Tonn, Panayotis Verginis, Malte von Bonin, Manja Wobus, Martin Bornhäuser, Tatyana Grinenko, Marianna Di Scala, Andres Hidalgo, Ben Wielockx, George Hajishengallis, Triantafyllos Chavakis
Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche
published pages: 3624-3639, ISSN: 0021-9738, DOI: 10.1172/jci92571
Journal of Clinical Investigation 127/10 2019-06-18
2019 Baomei Wang, Jong-Hyung Lim, Tetsuhiro Kajikawa, Xiaofei Li, Bruce A. Vallance, Niki M. Moutsopoulos, Triantafyllos Chavakis, George Hajishengallis
Macrophage β2-Integrins Regulate IL-22 by ILC3s and Protect from Lethal Citrobacter rodentium-Induced Colitis
published pages: 1614-1626.e5, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.01.054
Cell Reports 26/6 2019-08-29
2019 Ben Wielockx, Tatyana Grinenko, Peter Mirtschink, Triantafyllos Chavakis
Hypoxia Pathway Proteins in Normal and Malignant Hematopoiesis
published pages: 155, ISSN: 2073-4409, DOI: 10.3390/cells8020155
Cells 8/2 2019-08-29
2019 Michal Grzybek, Alessandra Palladini, Vasileia I. Alexaki, Michal A. Surma, Kai Simons, Triantafyllos Chavakis, Christian Klose, Ãœnal Coskun
Comprehensive and quantitative analysis of white and brown adipose tissue by shotgun lipidomics
published pages: 12-20, ISSN: 2212-8778, DOI: 10.1016/j.molmet.2019.01.009
Molecular Metabolism 22 2019-08-29

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