Project Details
Projekt
KFO 170: Early Pathogenesis of Wegener's Granulomatosis: From Innate Immunity with Granuloma Formation to Autoimmunity.
Subject Area
Medicine
Term
from 2007 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 33872855
The goal of the Clinical Research Unit is to investigate the early pathogenesis of Wegener's granulomatosis (WG), i.e. pathomechanisms resulting in granuloma formation and autoimmunity. WG is a systemic, chronic inflammatory disease of unknown etiology. WG is a model disease for analysing the evolution of an autoimmune disease from a misdirected inflammatory process. WG starts as granulomatous disease of the respiratory tract before it converts into a life- and/or organ-threatening, systemic autoimmune-vasculitis. While the pathomechanism of the autoimmune vasculitis appears to have been basically understood, mechanisms of the early pathogenesis have remained elusive (induction of granuloma formation, exogenous and endogenous factors governing granulomatous inflammation and autoimmunity).
Crucial questions of early WG-pathogenesis concern the induction of ANCA, i.e. vasculitis-associated, anti-neutrophile cytoplasmatic autoantibodies against "Wegener's autoantigen" proteinase 3 (PR3-ANCA). The specific aim is to find out why and where PR3 becomes the exclusive target auto-antigen and which factors (genetic and exogen influences) result in the formation of lymphoid follicles in the granulomatous inflammation, which has been implicated in developing autoimmunity in WG.
The induction of granulomatous inflammation in the respiratory tract and the postulated, subsequent formation of tertiary lymphoid structures are seen as one process in the early WG-pathogenesis. This process starts with granuloma formation in localised WG, followed by stepwise formation of lymphoid tissue in the WG-granuloma and induction of PR3-ANCA during the early systemic WG-phase. These processes have become the focus of distinct projects of our group.
Researchers from different disciplines within the Clinical Research Unit analyse cell systems and molecular structures of the innate and adaptive immunity. Special attention is being paid to "danger-receptors" and "danger-molecules" (e.g. PAR-2, PR3). Moreover, the role of exogenous and endogenous factors, dendritic cells and T-cells is studied with respect to granuloma formation and tertiary lymphoid tissue evolution in the WG-granuloma. '
Crucial questions of early WG-pathogenesis concern the induction of ANCA, i.e. vasculitis-associated, anti-neutrophile cytoplasmatic autoantibodies against "Wegener's autoantigen" proteinase 3 (PR3-ANCA). The specific aim is to find out why and where PR3 becomes the exclusive target auto-antigen and which factors (genetic and exogen influences) result in the formation of lymphoid follicles in the granulomatous inflammation, which has been implicated in developing autoimmunity in WG.
The induction of granulomatous inflammation in the respiratory tract and the postulated, subsequent formation of tertiary lymphoid structures are seen as one process in the early WG-pathogenesis. This process starts with granuloma formation in localised WG, followed by stepwise formation of lymphoid tissue in the WG-granuloma and induction of PR3-ANCA during the early systemic WG-phase. These processes have become the focus of distinct projects of our group.
Researchers from different disciplines within the Clinical Research Unit analyse cell systems and molecular structures of the innate and adaptive immunity. Special attention is being paid to "danger-receptors" and "danger-molecules" (e.g. PAR-2, PR3). Moreover, the role of exogenous and endogenous factors, dendritic cells and T-cells is studied with respect to granuloma formation and tertiary lymphoid tissue evolution in the WG-granuloma. '
DFG Programme
Clinical Research Units
Projects
- Einfluß endogener und exogener Faktoren auf die Grenzflächenläsion am respiratorischen Epithel bei Wegenerscher Granulomatose (Applicants Ambrosch, Petra ; Gottschlich, Stefan )
- Entwicklung ektoper lymphatischer Strukturen im WG-Granulom als Voraussetzung für Autoimmunität (Applicant Müller, Antje )
- Experimentelle WG-Initiierung durch Granulomtransfer in Pfp/Rag2-/- Mäuse (Applicant Ullrich, Sebastian )
- Genetische Suszeptibilität der Regulation initialer Entzündungsprozesse bei der WG (Applicant Wieczorek, Stefan )
- Memory T-Zell Dynamik bei Wegenerscher Granulomatose (Applicant Lamprecht, Peter )
- Memory T-Zell Dynamik bei Wegenerscher Granulomatose (Applicant Kabelitz, Dietrich )
- Molekulare Induktionsmechanismen der dendritischen Zellreifung durch Neutrophil Extracellular Traps (NETs) bei WG (Applicant Holle, Julia Ulrike )
- Molekulare Induktionsmechanismen des "Danger Rezeptors" Proteinase-aktivierter Rezeptor 2 (PAR-2) auf Dendritische Zellen (DC) (Applicant Ehlers, Stefan )
- Verwaltungsprojekt (Applicant Gross, Wolfgang L. )
- Z-Bereich: KFO-Leitung / Kohortenstudie: Risikostratefizierung - zelluläre Signaturen und Biomarker (Applicant Moosig, Frank )
- Zentralprojekt Z2: Projektübergreifendes Studienzentrum (Applicant Moosig, Frank )
Spokesperson
Professor Dr. Wolfgang L. Gross
