The spatial and temporal distribution of dendritic cells (DC) is essential for the initiation of specific immunity and tolerance. Patients with Wiskott Aldrich Syndrome (WAS) show loss of WAS protein (WASp) function, resulting in impaired immune cell migration and abnormal splenic architecture. Ongoing studies of the host laboratory suggest that DC migration to inflamed tissue and to draining lymphoid tissue is compromised and accompanied by exaggerated production of pro-inflammatory cytokines, such as IL-1 2 and IL-6 in vitro. We hypothesise that deficient DC migration may impair normal immune cell distribution in lymphoid tissue and influence subsequent immune function.
We therefore aim to determine the role of WASp in DC biology and its specific role in DC migration.
1. We will study the role of WASp in the distribution of DC subsets and their cytokine expression in response to TLR stimulation.
2. We will investigate whether and how WASp regulates the migration and localisation of DC in steady state and in inflammatory conditions.
3. We will use two-photon laser microscopy to study the real time migratory behaviour of WASp-/- DC and their interaction with other immune cells.
We expect this project to have profound impact on my scientific career and more in general in the field of DC biology. Better understanding of the role of WASp in DC migration and in immune function will provide better insight in the immunological pathogenesis of WAS and may provide important information for design of new therapies.
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