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Research Group Renné
Crosstalk of coagulation and inflammation
Aim
The central goal of the group is to analyze common principles, interactions and cross-talk between coagulation and inflammation, to identify novel therapeutic targets.
Scope of Research
Thromboinflammation • safe anticoagulation • contact system • polyphosphate
Research Projects
1. Functions and regulation of polyphosphate in mammalians
In mammals, inorganic polyphosphate (polyP) is a linear polymer of orthophosphate residues with emerging roles in hemostasis, inflammation, and cellular stress responses. PolyP can act as a procoagulant by activating factor XII and modulating fibrin structure, thereby influencing thrombus formation and stability. While the enzymatic machinery for polyP metabolism in mammals remains incompletely defined, we have generated ex vivo and in vivo models to analyze distribution, functions, predictive value as a biomarker, and regulation of the inorganic polymer in mice and humans.
2. The polyphosphate/factor XII-axis in thromboinflammatory disease
The polyphosphate/factor XII (polyP/FXII) axis plays a central role in thromboinflammatory disease by linking innate immunity with coagulation. PolyP released from activated platelets, mast cells, or damaged tissue activates FXII, initiating the contact pathway of coagulation and promoting thrombin generation. Beyond coagulation, FXII activation drives kallikrein-kinin signaling, contributing to vascular permeability and leukocyte recruitment. We analyze dysregulation of this axis in a range of disorders, including thrombosis, angioedema, and septic inflammation to highlight its potential as a therapeutic target.
3. Role of the factor XII-driven contact system in host defense
The factor XII (FXII)-driven contact system contributes to host defense by integrating coagulation, inflammation, and innate immunity. Upon activation by negatively charged surfaces such as microbial polyphosphates or neutrophil extracellular traps (NETs), FXII initiates the kallikrein-kinin cascade, leading to bradykinin release and increased vascular permeability, which facilitates immune cell recruitment to sites of infection or injury. Concurrently, FXII activation supports thrombus formation that can entrap pathogens and limit their dissemination. Moreover, recent evidence suggests that FXII modulates neutrophil function and cytokine release. We study the role of polyanions/FXII in innate immunity and their multifaceted role in coordinating immune responses during infection and tissue injury with impact on cardiovascular disease states.
Key Techniques
- In vivo and ex vivo coagulation analysis
- Technology to analyze and manipulate polyphosphate
- Biomarker analysis in humans and experimental animal models
Group Members
Publications
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Factor XII-driven coagulation traps bacterial infections
Nickel, K.F., Jämsä, A., Konrath, S., Papeddy, P., Butler, L.M., Stavrou, E.X., Frye, M., Gelderblom, M., Nieswandt, B., Hammerschmidt, S., Herwald, H., Renné, T.
J. Exp. Med.,2025, 222, e20250049. doi: 10.1084/jem.20250049. -
Sepsis-induced NET formation requires MYD88 but is independent of GSDMD and PAD4.
Englert H, Rangaswamy C, Kullik GA, Divivier M, Göbel J, Hermans-Borgmeyer I, Borgmeyer U, Mowen KA, Beerens M, Frye M, Mailer RK, Gelderblom M, Stavrou EX, Preston RJS, Schneider SW, Fuchs TA, Renné T.
FASEB J. 2025 Jan 15;39(1):e70301. doi: 10.1096/fj.202402514R. -
A single antibody targeting factor XII inhibits both thrombosis and inflammation.
Xu P, Zhang Y, Guo J, Li H, Konrath S, Zhou P, Cai L, Rao H, Chen H, Lin J, Cui Z, Ji B, Wang J, Li N, Liu DP, Renné T, Wang M.
Nat Commun. 2024 Sep 12;15(1):7898. doi: 10.1038/s41467-024-51745-4. -
Factor XII signaling via uPAR-integrin β1 axis promotes tubular senescence in diabetic kidney disease .
Elwakiel A, Gupta D, Rana R, Manoharan J, Al-Dabet MM, Ambreen S, Fatima S, Zimmermann S, Mathew A, Li Z, Singh K, Gupta A, Pal S, Sulaj A, Kopf S, Schwab C, Baber R, Geffers R, Götze T, Alo B, Lamers C, Kluge P, Kuenze G, Kohli S, Renné T, Shahzad K, Isermann B.
Nat Commun. 2024 Sep 11;15(1):7963. doi: 10.1038/s41467-024-52214-8 -
Targeting NETs using dual-active DNase1 variants.
Englert H, Göbel J, Khong D, Omidi M, Wolska N, Konrath S, Frye M, Mailer RK, Beerens M, Gerwers JC, Preston RJS, Odeberg J, Butler LM, Maas C, Stavrou EX, Fuchs TA, Renné T.
Front Immunol. 2023 May 23;14:1181761. doi: 10.3389/fimmu.2023.1181761.
Grants/Awards
- DFG, INST 337/93-1: Massenspektrometrisches Analysesystem
- Vetenskapsrådet, #02378: The contact system: an interface between coagulation, inflammation and innate immunity
- Preis der Deutschen Hochschulmedizin, Team VITT, Berlin (2022)
- Eberhard F. Mammen Award in Thrombosis and Haemostasis (2025)
Most important collaboration partners
- James O´Donnell, Dublin, Ireland
- Andreas Greinacher, Greifswald, Germany
- Bernhard Nieswandt, Würzburg, Germany
- Evi Stavrou, Cleveland, USA
- James Morrissey, Ann Arbor, USA
- Heiko Herwald, Lund, Sweden
- Lynn Butler, Tromsø, Norway