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Development and immune function of innate lymphoid cells

Applicant Finke Daniela
Number 153247
Funding scheme Project funding (Div. I-III)
Research institution Departement Biomedizin Universität Basel
Institution of higher education University of Basel - BS
Main discipline Immunology, Immunopathology
Start/End 01.05.2014 - 30.04.2017
Approved amount 372'000.00
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Keywords (10)

innate lymphoid cell; lymphoid tissue inducer cell; stem cell; development; cytokines; lineage commitment; innate response; immune system; transcription factor; TSLP

Lay Summary (German)

Lead
Die Entwicklung und Funktion von angeborenen LymphozytenDie angeborenen Lymphozyten sind Zellen des Immunsystems, die im Gegensatz zum erworbenen Immunsystem schnell und unspezifisch die Abwehr von Infektionen regulieren können. Das hier beschriebene Projekt soll zu einem besseren Verständnis der Herkunft und der Funktion dieser Zellen beitragen.
Lay summary

Inhalt und Ziel des Forschungsprojekts

 

In den letzten 10 Jahren konnten Zellen des angeborenen Immunsystems identifiziert werden, die sich in ihrer Produktion an regulatorischen Botenstoffen und in ihrer Bedeutung für die Immunabwehr unterscheiden. Es gibt Hinweise darauf dass diese angeborenen Lymphozyten mittels löslicher Proteine nicht nur eine Bedeutung für die Abwehr von Infektionen haben, sondern auch bei der Pathogenese von Entzündungen, Allergien und Tumoren eine Rolle spielen.

 

Wir untersuchen, ob angeborene Lymphozyten bei Entzündungen aktiviert werden und direkt auf andere Immunzellen einwirken. Darüber hinaus studieren wir, ob angeborene Lymphozyten eine Schutzfunktion für Organe haben. Wir wollen herausfinden, welche molekularen Mechanismen der Entwicklung und Aktivierung von angeborenen Lymphozyten zugrunde liegen. Die Ergebnisse können zu einem besseren Verständnis einer bislang wenig untersuchten Familie von Immunzellen beitragen.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Dieses Forschungsprojekt kann dazu beitragen Strategien zu entwickeln, angeborene Lymphozyten in Patienten mit Immundefekten oder mit chronischen Entzündungen (z.B. Asthma, Kolitis) therapeutisch zu nutzen.

 

 

Direct link to Lay Summary Last update: 25.04.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis.
Brasseit J Althaus-Steiner E Faderl M Dickgreber N Saurer L Genitsch V Dolowschiak T Li H Fi (2016), CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis., in Mucosal Immunol, 9(3), 689-701.
Cutting Edge: Innate Lymphoid Cells Suppress Homeostatic T Cell Expansion in Neonatal Mice.
Bank U Deiser K Finke D Hämmerling GJ Arnold B Schüler T. (2016), Cutting Edge: Innate Lymphoid Cells Suppress Homeostatic T Cell Expansion in Neonatal Mice., in J Immunol, 196(9), 3532-3536.
Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.
Baerenwaldt A von Burg N Kreuzaler M Sitte S Horvath E Peter A Voehringer D Rolink AG Finke (2016), Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice., in J Immunol, 196(6), 2561-2571.
Permissive roles of cytokines interleukin-7 and Flt3 ligand in mouse B-cell lineage commitment.
von Muenchow L Alberti-Servera L Klein F Capoferri G Finke D Ceredig R Rolink A Tsapogas P. (2016), Permissive roles of cytokines interleukin-7 and Flt3 ligand in mouse B-cell lineage commitment., in Proc Natl Acad Sci U S A, 113(50), E8122-E8130.
IL-7R signaling in regulatory T cells maintains peripheral and allograft tolerance in mice.
Schmaler M Broggi MA Lagarde N Stöcklin BF King CG Finke D Rossi SW. (2015), IL-7R signaling in regulatory T cells maintains peripheral and allograft tolerance in mice., in Proc Natl Acad Sci U S A., 112(43), 133350-133355.
Maintenance of Immune Homeostasis through ILC/T Cell Interactions.
von Burg N Turchinovich G Finke D. (2015), Maintenance of Immune Homeostasis through ILC/T Cell Interactions., in Front Immunol., 6, 416.
Activated group 3 innate lymphoid cells promote T-cell-mediated immune responses.
von Burg N Chappaz S Baerenwaldt A Horvath E Bose Dasgupta S Ashok D Pieters J Tacchini-Cotti (2014), Activated group 3 innate lymphoid cells promote T-cell-mediated immune responses., in Proc Natl Acad Sci U S A, 111(35), 12835-12840.

Collaboration

Group / person Country
Types of collaboration
Halin Winter, Cornelia, ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Antonius Rolink,Department of Biomedicine, Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Mohamed Bentires-Alj, FMI Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Hans Acha-Orbea, BIL, Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Christoph Mueller, Institute of Pathology, Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Simona, Rossi, DBM Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Kathy McCoy, MEM Institute for Research, University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Fabienne Tacchini-Cottier, Institute for Biochemistry, Epalinges Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Georg Holländer, Departement Biomedicine, Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Jim DiSanto, Pasteur Institute, Paris, France France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Jean Pieters, Biocenter, Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Andrew Macpherson, MEM Institute for Research, University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Burkhard Becher, Inst. Exp. Medicine, Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
EMBO Conference innate lymphoid cell, Berlin Individual talk Tissue-specific functions of ILC3s in regulating adaptive immunity 01.12.2016 Berlin, Germany Finke Daniela; Teufel Claudia;
International Immunology Congress, Melbourne, Australia Individual talk invited session chair 19.08.2016 Melbourne, Australia Finke Daniela;
PhD Symposium, Geneva Individual talk How do innate lymphoid cells regulate adaptive immunity? 24.06.2016 Geneva, Switzerland Finke Daniela;
PhD Retreat Poster The role of p38 MAPK signaling in lLC3 function 26.05.2016 Emmetten, Switzerland, Switzerland Finke Daniela;
Next Gen Immunology Poster Tissue-specific immune function of group 3 innate lymphoid cells 14.02.2016 Rehovet, Israel, Israel von Burg Nicole;
Innate Immunity Conference Talk given at a conference Crosstalk of innate lymphoid cells with the adaptive immune system 23.09.2015 Tübingen, Germany, Germany Finke Daniela;
65th SSAI meeting Basel Poster Flt3L controls the number of innate lymphoid cells in fetal and adult mice 13.03.2015 Basel, Switzerland, Switzerland Baerenwaldt Anne;
EMBO ILC conference Talk given at a conference Innate lymphoid cella and adaptive immunity 29.09.2014 Paris, France Finke Daniela;
DECIDE EU conference Talk given at a conference Innate lymphoid cells: development and function 15.09.2014 Basel, Switzerland Finke Daniela;
Summer course in Immunology - DB UNIL, Epalinges Individual talk Innate lymphoid cells: development and function 08.09.2014 Epalinger, Switzerland, Switzerland Finke Daniela;
Bellizona student retreat Talk given at a conference Innate lympohid cells: Development and function 13.05.2014 Engelberg, Switzerland Finke Daniela;


Self-organised

Title Date Place
Immunology Retreat Basel, Engelberg 31.10.2016 Engelberg, Switzerland
DBM Symposium 31.08.2016 Department of Biomedicine, Basel, Switzerland
Immunology Retreat Basel 02.11.2015 Engleberg, Switzerland
UKBB Forschertag 01.10.2015 Universitäts Kinderspital Beider Basel, Switzerland
Basel Immunology Focus Symposium - BIFS 31.08.2015 Basel, Switzerland, Switzerland
Oxford Minisymposium 11.11.2014 Oxford, UK, Great Britain and Northern Ireland
UKBB Forschertag 18.09.2014 Universitäts Kinderspital Beider Basel, Switzerland

Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Referat in der Gemeinde Riehen Talk 10.11.2016 Riehen, BS, Switzerland, Switzerland Finke Daniela;
Infoanlass Sponsoren UKBB Talk 22.06.2016 UKBB, Basel, Switzerland, Switzerland Finke Daniela;
Tag der Biomedizin Talk 09.04.2016 Basel, Switzerland, Switzerland Finke Daniela;
Kinderspital Zurich Forschungsretreat Talk 29.10.2015 Kindersptial, Zurich, Switzerland Finke Daniela;
Infoanlass Sponsoren UKBB Talk 01.07.2015 UKBB, Basel, Switzerland Finke Daniela;
Infoanlass Sponsoren UKBB Talk 09.07.2014 UKBB, Basel, Switzerland Finke Daniela;


Self-organised

Title Date Place
Open House for Suzy Rückert Foundation 09.02.2015 Basel, Switzerland

Associated projects

Number Title Start Funding scheme
172973 Deciphering the role of lymphoid-tissue networks and innate lymphoid cells for adaptive immunity 01.05.2017 Project funding (Div. I-III)
130674 Regulation of lymphoid tissue inducer cells during development and immune responses 01.02.2011 Project funding (Div. I-III)
136286 Recovery of intestinal homeostasis after microbial or immunological challenge 01.12.2011 Sinergia

Abstract

In the last decade, we have gained substantial knowledge on the control of the fate of innate lymphoid cells (ILCs), a group of lymphocytes including natural killer (NK) cells, which lack, in contrast to T and B cells, somatically rearranged antigen receptors. ILCs are characterized by producing cytokines analogous to Th1, Th2 and Th17 cell subsets and hence divide into 3 major families: 1) INFã-producing ILC1, 2) IL-4, -5, and-13-producing ILC2, and 3) IL-22 and -17-producing ILC3; the latter depend on the nuclear orphan receptor RORãt. Our previous research has shed light on how a subset of ILC3 named lymphoid tissue inducer (LTi) cells is regulated by cytokines. Less is known about their roles in early response to inflammation and in tissue remodelling. In addition various subsets of ILCs with immunogenic or tolerogenic function have been described that may depend on environmental cues. The identification of molecular pathways that regulate ILC differentiation and function is essential for a better understanding of how ILCs may contribute to protective or pathological responses.A main focus of this proposal is to discriminate immune functions of ILCs under steady-state and activating conditions in various organs and to identify pathways that regulate the differentiation of the cells. Using genetically modified mouse models as well as in vitro assays we will investigate whether ILCs can stimulate dendritic cells(DC), T cells and non-hematopoietic cells under steady-state or activating conditions. Finally we will study the transcriptional program regulating ILC development from hematopoietic precursor cells and their functional maturation.
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