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Project

Role of the cation channel TRPV4 in the maturation and migration of lung dendritic cells

The mammalian defence responses against foreign agents such as allergens and pathogens are largely based on an orchestrated interaction between detector and effector cells of the immune system. For instance, activation of dendritic cells leads to their maturation and migration to the regional lymph node, where they instruct T cells about the nature of the insult. We have found that mice lacking the calcium-permeable channel TRPV4 fail to recruit effector cells and to produce specific antibodies in response to exposure to the allergen house dust mite. After verifying that lymphocyte populations are not affected in these mice, we hypothesised that the lack of response in TRPV4-deficient animals may be due to malfunction of dendritic cells residing in the lung. To test this, we will determine the role of this channel in the maturation and migration of lung dendritic cells. We will first characterize the expression of TRPV4 in all the different subsets of lung dendritic cells and study the interaction between dendritic cells and neighbouring epithelial cells. Furthermore, using a mouse line with fluorescent dendritic cells we plan to determine the contribution of TRPV4 during the migration of DCs to the draining lymph node. This project will serve to unravel the role of TRPV4 in the immune responses in the airways, and to determine whether this channel could constitute a novel target for the treatment of airway inflammation.
 

Date:16 Aug 2017 →  Today
Keywords:Dendritic cells, TRPV4, TRP channels, asthma, inflammation
Disciplines:Allergology, Inflammation, Cell physiology, Respiratory medicine
Project type:PhD project