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Immuno-regulatory function of fibroblastic reticular cells of lymph nodes and airway smooth muscle cells of lungs

English title Immuno-regulatory function of fibroblastic reticular cells of lymph nodes and airway smooth muscle cells of lungs
Applicant Aurrand-Lions Michel
Number 112551
Funding scheme Project funding
Research institution Inserm Recherche en Cancérologie de Marseille Institut Paoli-Calmettes
Institution of higher education University of Geneva - GE
Main discipline Immunology, Immunopathology
Start/End 01.04.2006 - 31.10.2009
Approved amount 296'000.00
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Keywords (3)

inflammation; leukocyte migration; chronic inflammatory diseases

Lay Summary (English)

Lead
Lay summary
Immune response requires coordinated migration and positioning of immuno-competent cells in the organism. Leukocytes reach their destination by traveling through a network of channels that are formed by lymphatic and vascular endothelial cells. This has prompted many groups to consider that leukocyte migration is mainly dependent on cytokines and cognate interactions between circulating leukocytes and endothelial cells. It is in this context that most of the studies have focused on endothelial adhesion molecules such as ICAMs, VCAM-1, PECAM-1, or JAMs.
We have cloned and characterized JAM-B and JAM-C, which are involved in leukocyte adhesion and transmigration across endothelial cells. However, preliminary results in vivo prompt me to revisit the immuno-regulatory function of JAM-C in the light of its expression on sinus lining cells(SLCs) of lymph nodes and airway smooth muscle cells (ASM) of the lungs.
Indeed, recent studies have highlighted the role played by micro-environmental cells in the establishment and maintenance of micro-environmental "niches" favoring accumulation and retention of leukocytes in organs. Expression of adhesion molecules and secretion of cytokines are the major mechanisms by which parenchymal cells regulate the immune response. We thus propose to identify the function of JAM-C expression on SLCs and ASM cells. In addition, new adhesion molecules specifically expressed by SLCs and ASM cells and the immuno-regulatory pathways acting in these cells will be identified.
For this purpose, the role of JAM-C expression on ASM cells will be tested in vivo and in vitro. Airway hyper-responsiveness of JAM-C-/- mice will be explored and gene expression in primary ASM cells isolated from control orJAM-C-/- mice will be compared. As complementary approach, we will characterize new antibodies that we have generated against SLCs of lymph nodes and which recognize ASM cells but not endothelial cells. Combining these two approaches give a molecular basis for the putative immuno-regulatory mechanisms taking place in micro-environmental cells.
This will be of invaluable help in designing new therapeutic strategies aiming to target micro-environmental cells in chronic diseases such as ASM cells in asthma.
Direct link to Lay Summary Last update: 21.02.2013

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