Project: Systems medicine approach to minimize macrophage-associated interstitial fibrosis and tubular atrophy in renal allograft rejection

Acronym	Sys-MIFTA (Reference Number: JTC1_81)
Duration	01/05/2016 - 31/10/2019
Project Topic	Interstitial fibrosis and tubular atrophy (IF/TA) are major clinical challenges in kidney transplantation. Immunological knowledge on acute graft rejection and its clinical management have substantially improved, while the cumulative effects resulting in IF/TA- associated functional decline remain poorly understood. Systems medicine opens a new avenue towards unraveling these complex interactionsinvolving chronic cellular and humoral rejection, interstitial inflammation, and macrophage-mediated tissue remodeling processes. Alternatively activated macrophages play a central role in this complex network of cellular interactions, regulating T-cell behavior in the tissue microenvironment, inducing tissue repair and remodeling effects, and conferring a delicate equilibrium between immunosuppressivebeneficial and fibrosis-inducing detrimental effects. Sys-MIFTA will translate improved understanding of this network into tangible benefit for patients and cost-efficient, evidence-based use of currently emerging targeted immunomodulatory therapies. Key is integration of dynamic mathematical models of macrophage-associated immunological and metabolic regulation with advanced biopsy evaluation and ongoing clinical research to dissect processes in the renal interstitium that converge into IF/TA. Iterative model validation and improvement will be performed in the framework of a long standing protocol biopsy program and ongoing clinical studies. The interdisciplinary approach integrates systems immunology with advanced image analysis, digital pathology, basic immunology and clinical research. It will for the firsttime enable integration of advanced mathematical models and comprehensive digitally captured spatio-temporal information in clinical transplantation medicine. Sys-MIFTA paves the way towards innovative, participatory and predictive transplantation medicine, preventing morbidity and creating value by increasing efficacy of personalized immunomodulatory therapy.
Network	ERACoSysMed
Call	1st Call: European Research Projects to demonstrate the feasibility and benefits of systems medicine

Project partner

Number	Name	Role	Country
1	Hannover Medical School	Coordinator	Germany
2	Radboud University Medical Center	Partner	Netherlands
3	Istituto Clinico Humanitas IRCCS	Partner	Italy
4	University of Strasbourg	Partner	France
5	TU Dresden	Partner	Germany
6	Weizmann Institute of Science	Partner	Israel