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Junctional adhesion molecules, versatile players in inflammatory immune reactions

English title Junctional adhesion molecules, versatile players in inflammatory immune reactions
Applicant Imhof Beat A.
Number 120184
Funding scheme Project funding
Research institution Département de Pathologie et Immunologie Faculté de Médecine / CMU Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Immunology, Immunopathology
Start/End 01.04.2008 - 31.03.2011
Approved amount 653'459.00
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Keywords (5)

endothelium; cell adhesion; leukocyte migration; adhesion molecule; cell junctions

Lay Summary (English)

Lead
Lay summary
We are interested in the pathology of leukocyte migration, inflammatory diseases and tumor angiogenesis. Simultaneously with other laboratories we discovered and cloned the vascular adhesion molecules JAM-B and JAM-C. Expression and production of recombinant JAM-C enabled the development of a large panel and monoclonal and polyclonal antibodies. We produced transgenic mice over-expressing JAM-C in the vasculature by insertion of a vascular promoter (tie2) and we have JAM-C and JAM-B deficient mice. Using these reagents and the gene modified animals we showed JAM-C involved in immune responses against microorganisms preventing pneumonia. Furthermore, antibodies against JAM-C reduced the severity of acute and chronic inflammatory pathologies such as pancreatitis, peritonitis, vascular restenosis or rheumatoid arthritis. These effects of JAM-C seem to be due to its role in leukocyte transendothelial migration. The molecule forms a vascular barrier for tissue leukocytes returning back to the blood i.e. it contributes to the one-way traffic observed during leukocyte homing. Accordingly, we have evidence for JAM-C being a polarity protein that binds to polarity complex proteins. As JAM-C is also expressed by differentiating spermatides it is interesting to learn that polarization of these cells is hampered in JAM-C deficient mice and male animals are sterile. Furthermore, JAM-C seems to play a role in junctions of Schwann cells of the peripheral neural system leading to defective nerve conduction and motor abnormalities. Thus, Jam-C is a versatile junctional molecule implicated in several biological functions.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
129700 Role of dendritic cell subsets in Leishmania infection 01.05.2010 ProDoc
135701 Junctional adhesion molecules, versatile players in inflammatory immune reactions 01.04.2011 Project funding
100697 The role of junctional adhesion molecules in leukocyte transendothelial migration 01.04.2003 Project funding

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