DC-LYMPH
The Role of Lymphatic Vessels in Dendritic Cell Homing and Maturation
| Coordinatore | ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | Switzerland [CH] |
| Totale costo | 1˙730˙966 € |
| EC contributo | 1˙730˙966 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2007-StG |
| Funding Scheme | ERC-SG |
| Anno di inizio | 2008 |
| Periodo (anno-mese-giorno) | 2008-05-01 - 2013-04-30 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Organization address
address: BATIMENT CE 3316 STATION 1 contact info |
CH (LAUSANNE) | hostInstitution | 0.00 |
| 2 |
ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Organization address
address: BATIMENT CE 3316 STATION 1 contact info |
CH (LAUSANNE) | hostInstitution | 0.00 |
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Obiettivo del progetto (Objective)
'Dendritic cell (DC) activation and homing from the periphery to lymph nodes is a critical first event in the immune response. It involves upregulation of the chemokine receptor CCR7 and chemoinvasion towards lymphatic vessels. Despite its critical importance in adaptive immunity, the mechanisms of DC migration towards and entry into lymphatics are still poorly understood; this severely limits new therapeutic strategies for immunomodulation and even strategies for treating lymphedema, which is exacerbated by poor immune functioning. We propose a battery of physiological, cell-biological, molecular, and computational studies to determine both the mechanisms of DC homing to lymphatic vessels and how DCs modulate lymphatic function. We approach this from the perspectives of both the DC and the lymphatic vessel. Regarding the DC, we will examine computationally and experimentally how draining flows toward the lymphatic alter their migration tactics and test our hypothesis that DCs possess a biomolecular flow-detector network (which we refer to as autologous chemotaxis) and are thus able to sense the direction of the subtle flow of fluid toward the lymphatics. Regarding the lymphatic vessel, we will elucidate how biochemical and biophysical inflammatory signals regulate their drainage function, alter cell-cell adhesions and overall permeability, and alter adhesion receptors to facilitate DC homing and entry. Finally, we will examine DC migration in mice with dysfunctional lymphatics and explore strategies to improve immune response. These will be carried out in 4 main projects, and will complement our recent work in lymphatic functional biology as well as our more therapeutic investigations in DC targeting and activation (Reddy et al., Nature Biotechnol., 2007). This deeper knowledge of mechanisms of DC-lymphatic cross-talk in a relevant biophysical context will enable our long-term goal of rational design for therapeutic immunomodulation and lymphedema.'