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Regulation of immune responses by pro-inflammatory cytokines and co-stimulatory receptors

Applicant Kopf Manfred
Number 100233
Funding scheme Project funding
Research institution Gruppe Umwelt-Biomedizin Institut für Integrative Biologie Departement Umweltwissenschaften
Institution of higher education ETH Zurich - ETHZ
Main discipline Immunology, Immunopathology
Start/End 01.01.2004 - 31.12.2008
Approved amount 628'752.00
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Keywords (11)

co-stimulatory molecules; B7-CD28 superfamily; ICOS; CD40; IL-1; IL-6; ETA-1; IL-16; dendritic cells; T cell activation; Th1/Th2 development

Lay Summary (English)

Lay summary
Cytokines are key players in shaping immune responses against foreign invaders and self -antigens regulating the induction of effective immunity and tolerance. Our group has a long-standing interest in characterizing the role of cytokines in innate and adaptive immunity against various pathogens and their involvement in inflammatory diseases (e.g. asthma, myocarditis, pneumonitis, emphysema) in vivo. Cytokines such as IL-1, IL-6, IL-18, and IL-12 secreted by cell of the innate immune system upon infection induce inflammatory responses directly by activation of phagocytes and indirectly by regulating T helper subset differentiation into Th1, Th2, and Th17 cells. We and others have previously shown thatTh1 type IFN-g responses play a key role to ward off infections with bacteria, protozoa, and fungi, while Th2 type IL-4/IL-13 responses are required for expulsion of nematodes. More recently, Th17 cells characterized by production of IL-17 have been involved in autoimmunity.Specifically, we have shown that autoimmune myocarditis is dependent onIL-23 and IL-17. We currently investigate the role of GM-CSF in development of IL-17-mediated myocarditis.
Recently, we have generated mice lacking the cytokines IL-1d, IL-16, andIL-21 receptor by genetic engineering. Using these mice, we are investigating the role of the respective cytokines in infection with viruses (i.e. influenza virus, LCMV), gastrointestinal nematodes, and the protozoan parasite Leishmania major. Furthermore, we are characterizing the role of these cytokines in Th17 mediated heart autoimmunity and Th2 mediated asthmatic responses such as pulmonary eosinophil infiltration, airway hyperresponsiveness, and mucus production. We expect that these results contribute to the understanding of the respective human diseases and provide novel therapeutic approaches.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants


Associated projects

Number Title Start Funding scheme
124922 Effects of Interleukin-21 on T cell responses and diseases 01.07.2009 Project funding