Regulation of vascular inflammation in immunity and metabolic disease
Previous and Current Research
The scientific focus of the group of Prof. Chavakis is in the field of Innate Immunity and Immunometabolism especially on mechanisms contributing to chronicity of inflammation.
We aim at identifying inflammatory mechanisms that are involved in the regulation of chronic inflammation in the context of metabolic-inflammatory pathologies (insulin resistance, type 2 diabetes, NAFLD), inflammatory bone loss and cancer. In addition, we study how cellular metabolism regulates innate immune cell generation (myelopoiesis) and activation in the context of innate immune memory as well as emergency hematopoiesis.
At the molecular level, our group has identified molecular mechanisms governing adhesive interactions contributing to leukocyte recruitment and activation as well as resolution of inflammation. For instance, we have identified an endogenous inhibitor of the leukocyte adhesion cascade, developmental endothelial locus-1 (DEL-1). DEL-1 antagonizes IL-17-dependent inflammation and promotes resolution of inflammation as well. Additionally, we study the molecular mechanisms of the crosstalk between inflammation and metabolism at the cellular and systemic organism level. For instance, we have identified an immunometabolic crosstalk that is involved in the modulation of hematopoietic progenitor cells in the context of trained immunity.
Future Projects and Goals
We are trying to understand the connection between inflammation and metabolism at multiple levels. In particular, we analyse mechanisms underlying inflammatory cell accumulation and activation in metabolic organs (e.g. adipose tissue, liver). Additionally, we investigate mechanisms regulating resolution of inflammation, e.g. the phagocytic clearance of apoptotic cells by macrophages Moreover, we study alterations in the bone marrow in response to inflammation and in the context of trained innate immunity.
Methodological and Technical Expertise
- Experimental models of disease
- Acute Inflammation
- Chronic Inflammation
- Diet-induced obesity, Insulin resistance and non-alcoholic fatty liver disease
- Real-time RT-PCR
- Transcriptomic analysis
- Epigenomic analysis
- Metabolomic analysis
- Fluorescent immunocytochemistry – confocal microscopy
- Flow cytometry analysis
- Molecular cloning
- Primary cell isolation and culture
- Cell adhesion and migration
- Assays for leukocyte activation
- Biochemistry: Western Blot
Kourtzelis I, Li X, Mitroulis I, Grosser D, Kajikawa T, Wang B, Grzybek M, von Renesse J, Czogalla A, Troullinaki M, Ferreira A, Doreth C, Ruppova K, Chen LS, Hosur K, Lim JH, Chung KJ, Grossklaus S, Tausche AK, Joosten LAB, Moutsopoulos NM, Wielockx B, Castrillo A, Korostoff JM, Coskun Ü, Hajishengallis G*, Chavakis T*
DEL-1 promotes macrophage efferocytosis and clearance of inflammation.
Nature Immunology; 20:40–49 (2019)
*contributed equally as senior authors
Mitroulis I, Ruppova K, Wang B, Chen LS, Grzybek M, Grinenko T, Eugster A, Troullinaki M, Palladini A, Kourtzelis I, Chatzigeorgiou A, Schlitzer A, Beyer M, Joosten LAB, Isermann B, Lesche M, Petzold A, Simons K, Henry I, Dahl A, Schultze JL, Wielockx B, Zamboni N, Mirtschink P, Coskun Ü, Hajishengallis G*, Netea MG*, Chavakis T*
Modulation of myelopoiesis progenitors is an integral component of trained immunity.
Cell; 172:147–161 (2018)
*contributed equally as senior authors
Chung KJ, Chatzigeorgiou A, Economopoulou M, Garcia-Martin R, Alexaki VI, Mitroulis I, Nati M, Gebler J, Ziemssen T, Goelz SE, Phieler J, Lim JH, Karalis KP, Papayannopoulou T, Blüher M, Hajishengallis G, Chavakis T
A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity.
Nature Immunology; 18:654–664 (2017)
Economopoulou M, Langer HF, Celeste A, Orlova VV, Choi EY, Ma M, Vassilopoulos A, Callen E, Deng C, Bassing CH, Boehm M, Nussenzweig A, Chavakis T
Histone H2AX is integral to hypoxia-driven neovascularisation
Nature Medicine; 15.553–8 (2009)
Choi EY, Chavakis E, Czabanka MA, Langer H, Fraemohs L, Economopoulou M, Kundu RK, Orlandi A, Zheng YY, Prieto DA, Ballantyne CM, Constant SL, Aird W, Papayannopoulou T, Gahmberg CG, Udey MC, Vajkoczy P, Quertermous T, Dimmeler S, Weber C, Chavakis T
Del-1, an endogenous leukocyte endothelial adhesion inhibitor, limits inflammatory cell recruitment
Science; 322:1101–04 (2008)