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Identification of adhesion molecules involved in dendrtic cell migration into lymphatics

English title Identification of adhesion molecules involved in dendrtic cell migration into lymphatics
Applicant Halin Cornelia
Number 116128
Funding scheme Project funding (Div. I-III)
Research institution Institut für Pharmazeutische Wissenschaften ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Immunology, Immunopathology
Start/End 01.05.2007 - 31.07.2010
Approved amount 239'372.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Cardiovascular Research

Keywords (5)

leukocyte transmigration; dendritic cells; microarrays; activated lymphatic endothelium; lymphatic endothelial cells

Lay Summary (English)

Lead
Lay summary
Considerable knowledge has been gathered on the migration of leukocytes from blood vessels into tissues, but the processes governing leukocyte, in particular dendritic cell (DC), migration from peripheral tissues into lymphatics is much less well understood. Even so, it is well established that the migration of antigen-presenting DCs from peripheral tissues to lymph nodes via lymphatics plays a key role in initiating adaptive immune responses. DC migration likely involves interactions of DC-expressed adhesion molecules with their counter-receptors on lymphatic endothelial cells (LECs), but only few such interactions have been identified to date. Working HypothesisFrom the blood vascular system it is known that many of the adhesion molecules and chemokines that are upregulated on activated blood vascular endothelial cells (BECs) under inflammatory conditions are involved in the recruitment of leukocytes to peripheral tissues (e.g. E-selectin, P-selectin, VCAM-1, ICAM-1). One can assume that, similar to BECs, those adhesion molecules that are either up- or downregulated on LECs are potentially involved in leukocyte interactions with lymphatic endothelium and in the overall process of leukocyte migration into or within lymphatics. Specific AimsThe proposed project seeks to address how DCs interact with LECs during the process of transmigration into lymphatic vessels. Furthermore, it seeks to characterize the phenotype of activated LECs, which is practically unknown to date.Experimental Design and / or MethodsBy comparing the gene expression profiles (by microarray analysis) of LECs that have been isolated by FACS-sorting from either inflamed or uninflamed murine skin, we seek to identify genes (e.g. adhesion molecules or chemokines) that are differentially expressed under these two conditions. The involvement of these candidate genes in DC transmigration through lymphatic endothelium will subsequently be investigated in in vitro transmigration assays and in adoptive transfer experiments in mice.Expected Value of the Proposed Project Overall, the proposed project contributes to enhancing our understanding of the process and the molecules involved in leukocyte transmigration across lymphatic barriers. Such knowledge will likely be of great value for therapeutic strategies seeking to modulate immune responses, such as for vaccinations or during chronic inflammatory autoimmune diseases.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
121400 In vivo Biolumineszenz und Fluoreszenz Bildgebungssystem: IVIS Spectrum 01.07.2008 R'EQUIP
156269 Elucidating the mechanism and the functional significance of leukocyte migration through afferent lymphatic vessels 01.01.2015 Project funding (Div. I-III)

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