TI-3: The Complement Network as a Novel target in CIBD
Coordinators:J.Khl(UzL),C.Kemper(UzL),E.Schmidt(UzL)
Theimmunesystemandthenetworksthatregulateitdeterminetheoriginandthedevelopmentofchronicinflammatorybarrierdiseases(CIBD).Theso-calledcomplementsystemispartoftheinnateimmunesystem,andthusanintegralpartoftheseregulatorynetworks.AgoalofTI-3istouncovertheunderlyingmechanismsbehindthecomplexactivationandregulationofthecomplementsysteminpemphigoiddiseasesasprototypicalinflammatorydiseases.Pemphigoiddiseasesareautoimmunediseasesoftheskin,inwhichblistersanderosionsformontheskinandmucousmembranesclosetothesurface.ThefindingsfromTI-3shouldpavethewayfornew,individualizeddiagnosticandtherapeuticapproachestotheseinflammatorydiseases.
What does this research area’s work build on?
Thecomplementsystemconsistsofsolubleandcell-boundmoleculeswhichnetworkwithotherhumoralandcellularcomponentsoftheinnateimmunesystem.MembersofTI-3haverecentlydemonstratedthatthecomplementsystemisnotonlyaserumsystem,butthatmanyimmunecellscanproducecomplementproteinslocallyintissue,dividethemandactivatethemwithinthecellbyspecificproteases.Inordertobetterunderstandthesenewfunctionsofthesystem,theTI-3researchershavedevelopeduniquetoolsthatprovidedetailedinsightsintotheregulationofthesystem.Theseareimportantforunderstandingtheimmunemechanismswhichunderliechronicinflammatorydiseases.Thus,autoreactiveIgGantibodiesoftencausemassivelocaland/orsystemiccomplementactivationinpatientswithpemphigoiddiseases,butthisvariesconsiderablybetweenindividualpatients.
What are the main research objectives?
Animportantgoalisthecharacterizationofthesystemicandlocalcomplementactivation,andtheexpressionofcomplementreceptorsinexperimentalandhumanautoimmunediseasesoftheskin.Thisknowledgeshouldbeusedtoidentifythepatientgroupswherethecomplementactivationdrivestheauto-antibody-mediatedskininflammation.Furthermore,theeffectsoflocalcomplementproductionandactivationontheactivationandregulationofimmunologicalnetworksshouldbedeterminedinthecontextofpemphigoiddiseases.Inaddition,inTI-3thebilateralrelationshipbetweenlocalcomplementproductionandactivationandthecompositionanddiversityoftheskinmicrobiomeshouldbedefined,sincethemicrobiomeinteractsextensivelywiththeinnateandacquiredimmunesystem.
What makes this research area special?
Withthecomplementsystem,thisresearchareafocusesonapartoftheinnateimmunesystemwhich-inthecontextofchronicinflammatorydiseases-haspreviouslyonlybeeninsufficientlyresearchedandunderstood.Byusingnewreportersystemsforthedetectionanddifferentialactivationofthecomplementsystem,thisresearchareaoffersnewapproachestoindividualdiagnosticsandtreatmentofchronicinflammatorydiseases.Thisisbeinginvestigatedexperimentallyandclinicallyindifferentgroupsofpatientswithpemphigoiddisorders.
What does the research area contribute to precision medicine in chronic inflammation?
TheresultsfromTI-3shouldleadtoanewclassificationofpatientswithpemphigoiddiseaseswhichisbasedonthepatternsoftheirlocalcanonicalandnon-canonicalcomplementactivation.Detailedmechanisticinsightsintotheactivationofcomplement-mediatedsignalingpathwaysshouldbeusedinordertodevelopnewtherapeuticapproacheswhichblockthedefinedcomplementsignalingpathwaysand/orreceptors.AspecificcomplementinhibitordevelopedintheKhllaboratoryisavailableforthispurpose.Inaddition,thebilateralrelationshipbetweenthelocalcomplementactivationandthecompositionanddiversityofthemicrobiomeshouldbedecoded,withtheaimofspecificallymodulatingthisinteraction.
Cooperation with other research areas in the cluster
TI-3workscloselywithRTFsI,IIIandIV,fromwhichitreceivesthedatathatdetailstheindividualgenomic,metagenomicandimmunophenotypicdifferencesbetweenthepatients.Forthemicrobiomeanalysisoftheskininexperimentalpemphigoidmodels,aswellasfrompemphigoidpatients,TI-3collaboratescloselywithTI-1,CD-5andtheCCIMs.
Members
Dr. Nadia Andreani
Associated member
Max Planck Institute for Evolutionary Biology
Institute of Experimental Medicine
AG Prof. Baines
Prof. Dr. John Baines
Full member
Max Planck Institute for Evolutionary Biology
Institute of Experimental Medicine
Evolutionary Genomics
Dr. rer. nat. Corinna Bang
Assocciated member
Kiel University
Institute of Clinical Molecular Biology
AG Prof. Franke
Prof. Dr. med. Thorsten Bartsch
Full member
UKSH Campus Kiel
Department of Neurology
Prof. Dr. Christoph Becker-Pauly
Full member
Kiel University
Institute of Biochemistry
Degradomics of the Protease Web
Dr. Meriem Belheouane
Associated member
Research Center Borstel - Leibniz Lung Center
Evolution of the Resistome
Priority Research Area Infections
AG Prof. Merker
PD Dr. Katja Bieber
Associated member
UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Prof. Dr. Hauke Busch
Full member
UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
System Biology of Inflammatory Diseases
Prof. Dr. Christof Dörfer
Full member
UKSH Campus Kiel
Department of Dental Conservation Customer and Periodontology
Prof. Dr. Marc Ehlers
Full member
UKSH Campus Lübeck
Institute of Medical Nutrition Science
Immunology and Glycoanalytics
Dr. rer. nat. Maren Falk-Paulsen
Associated member
Kiel University
Institute of Clinical Molecular Biology
RG Prof. Rosenstiel
Prof. Dr. rer. nat. Andre Franke
Full member
Kiel University
Institute of Clinical Molecular Biology
Genetics & Bioinformatics
Prof. Dr. Timo Gemoll
Associated member
UKSH Campus Lübeck
Department of General Surgery
Prof. Dr. med. Regine Gläser
Full member
UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology
Dr. rer. nat. Simon Graspeuntner
Associated member
UKSH Campus Lübeck
Department of Infectious Diseases and Microbiology
AG Prof. Rupp
Martina Guggeis
Associated member
Kiel University
Institute of Clinical Molecular Biology
AG Prof. Rosenstiel
Dr. rer. hum. biol. Yask Gupta
Associated member
UKSH Campus Lübeck
Institute for Inflammation Medicine
AG Prof. Thaçi
Prof. Dr. rer. nat. Jürgen Harder
Full member
UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology
Prof. Dr. rer. nat. Markus Hoffmann
Full member
UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology
Prof. Dr. Saleh Ibrahim
Full member
UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Genetics of Inflammatory Diseases
Lea Järke
Associated member
Kiel University
Institute of Clinical Molecular Biology
AG PD Sommer
Prof. Dr. Christoph Kaleta
Full member
UKSH Campus Kiel
Institute of Experimental Medicine
c/o Transfusion Medicine
Dr. rer. nat. Anika Kasprick
Associated member
UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
AG Prof. Ludwig
Prof. Dr. rer. nat. Ben Krause-Kyora
Full member
Kiel University
Institute of Clinical Molecular Biology
Ancient DNA Research
Prof. Dr. med. Matthias Laudes
Full member
UKSH Campus Kiel
Institute of Diabetes and Clinical Metabolic Research
PD Dr. Yves Laumonnier
Associated member
University of Lübeck
Institute for Systemic Inflammation Research
Prof. Dr. Ralf Ludwig
Full member
UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Model Systems of Inflammatory Skin Diseases
Prof. Dr. rer. nat. Silke Meiners
Full member
Kiel University
Institute of Experimental Medicine
c/o Research Center Borstel - Leibniz Lung Center
Immunology and Cell Biology
Priority Research Area Chronic Lung Diseases
Prof. Dr. Matthias Merker
Full member
Research Center Borstel - Leibniz Lung Center
Evolution of the Resistome
Priority Research Area Infections
Prof. Dr. Ulrich Mrowietz
Full member
UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology
Psoriasis-Center
Dr. Wiebke Prüßmann
Associated member
UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology
Prof. Dr. Gabriela Riemekasten
Full member
UKSH Campus Lübeck
Department of Rheumatology and Clinical Immunology
Prof. Dr. med. Christoph Röcken
Full member
UKSH Campus Kiel
Institute of Pathology
Prof. Dr. Stefan Rose-John
Full member
Kiel University
Institute of Biochemistry
Cytokine and Metalloproteinase Research
Prof. Dr. med. Philip Rosenstiel
Full member
Kiel University
Institute of Clinical Molecular Biology
Molecular Cell Biology
Prof. Dr. Jan Rupp
Full member
UKSH Campus Lübeck
Department of Infectious Diseases and Microbiology
Prof. Dr. Christian Sadik
Full member
UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology
Innate immunity
Prof. Dr. rer. nat. Alexander Scheffold
Full member
UKSH Campus Kiel
Department of Immunology
Prof. Dr. Dr. Enno Schmidt
Full member
UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Translational Research
Prof. Dr. rer. nat. Ruth Schmitz-Streit
Full member
Kiel University
Institute of General Microbiology
Molecular Biology of Microorganisms
Prof. Dr. med. Stefan Schreiber
Spokesperson
Kiel University
Institute of Clinical Molecular Biology
Prof. Dr. Hinrich Schulenburg
Full member
Kiel University
Institute of Zoology
Evolutionary Ecology and Genetics
Prof. Dr. Christian Sina
Full member
UKSH Campus Lübeck
Institute of Medical Nutrition Science
Dr. rer. nat. Felix Sommer
Full member
UKSH Campus Kiel
Institute of Clinical Molecular Biology
Functional Host-Microbiome Research
Prof. Dr. Diethard Tautz
Full member
Max Planck Institute for Evolutionary Biology
Evolutionary Genetics
Dr. Daniel Unterweger
Full member
Max Planck Institute for Evolutionary Biology
Institute of Experimental Medicine
Prof. Dr. med. Thomas Valerius
Full member
UKSH Campus Kiel
Department of Internal Medicine II
Stem Cells and Immunotherapy
Dr. Artem Vorobyev
Associated member
UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology
Dr. Georg Wätzig
Associated member
UKSH Campus Kiel
Institute of Clinical Molecular Biology
Prof. Dr. Stephan Weidinger
Full member
UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology
