CX3CR1 and CX3CL1 in allergic diseases – CX3CR1

Allergic asthma is a T helper (Th) 2-dominated disease of the lung. In asthmatic patients, a fraction of CD4+ T cells express the CX3CL1 receptor CX3CR1, and its ligand CX3CL1 expression is increased in airway smooth muscle, lung endothelium and epithelium upon allergen challenge. In a recent study published in Nature Medicine, we have demonstrated that the expression of CX3CR1 by CD4+ T cells is required for the development of allergic asthma in mice. CX3CR1 is not required for the recruitment of allergen-specific CD4+ T cells into the airways, but for their survival in the inflamed lungs. We also showed that curative treatment with local administration of a CX3CL1 antagonist prevents the disease and induces allergen-specific CD4+ T cell death. Allergen-specific CD4+ T cells do not express CX3CR1 in the periphery but in airways, probably as the result of exposure to soluble factors present in inflamed lung.
In this proposal, we will aim at (1) identifying the signaling pathways by which CX3CL1 induces T helper cell survival, (2) investigating the role of CX3CL1-expressing airway epithelial and endothelial cells in allergic asthma, (3) investigating the role of CX3CR1-expressing Th1, Th2 and Th17 cells in atopic dermatitis, and we will identify which cell type expressing CX3CL1 is involved. Last, we will attempt to identify the molecules and the transcription factors that are responsible for CX3CR1 upregulation in the inflamed lungs.
Altogether, these experiments will provide new insights into the immunobiology of CX3CR1, and should reinforce CX3CR1 as therapeutic target against allergic diseases.