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Content archived on 2024-05-29

CCL18 - a susceptibility gene for atopic eczema regulated by host-microbe interactions?

Objective

Atopic disorders are a group of increasingly common multifactorial chronic diseases, which cause inflammatory and degenerative changes in the skin and mucosal surfaces. Among those diseases, atopic eczema represents the most prevalent condition affecting u p to 22% of the paediatric and 1-3% of adult population.

The aetiology of atopic eczema involves environmental, genetic and immunological factors. For the prevention and treatment of this disease, advances are needed in the identification of susceptibility factors, disease markers and therapeutic targets. The skin-specific trafficking of inflammatory cells during atopic eczema is regulated by chemokines. CCL18 is the most highly and specifically expressed chemokine in atopic eczema.

We will analyze the role of single nucleotide polymorphisms in the CCL18 gene in the susceptibility for atopic eczema using an exceptional size of DNA sample collection (n = 3111) obtained from atopic and non-atopic individuals. Furthermore, we will analyze the methylation status of CCL18 gene in atopic eczema patients in comparison to healthy controls.

Additionally, we will examine whether the serum level of CCL18 correlates with disease severity, therapeutic treatments and trigger factors, using large number of well-characterize d samples obtained from atopic eczema patients and healthy individuals. The host's previous work demonstrated an important role for the opportunistic yeast Malassezia in triggering the IgE- and T cell-mediated inflammation in atopic eczema patients.

Hence, we will investigate whether Malassezia allergens can be responsible for the elevated level of CCL18 in atopic lesional skin by examining CCL18 expression in all relevant structural cells of the skin as well as in dendritic cells and mast cells.

This project aims to increase our knowledge about susceptibility factors, disease markers and the pathogenesis of atopic eczema, which may contribute to prospective prevention studies and new treatment strategies.

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Topic(s)

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Call for proposal

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FP6-2004-MOBILITY-5
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Funding Scheme

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EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

KAROLINSKA INSTITUTET
EU contribution
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Total cost

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