Wiskott-Aldrich syndrome investigated

Recent findings from the ICGEB Cellular Immunology lab published this week in JEM

The latest finding from the Cellular Immunology Group, ICGEB Trieste, headed by Federica Benvenuti has been published this week in The Journal of Experimental Medicine and represents an important step forward in the diagnosis and treatment of Wiskott-Aldrich syndrome, a rare form of immunodeficiency.

This study shows the mechanisms by which unrestrained type-I interferon production by plasmacytoid dendritic cells deficient for the Wiskott-Aldrich syndrome protein cause the emergence of autoimmunity, and reveals a previously unknown role for actin in controlling the innate functions of plasacytoid dendritic cells.

Tight regulation of the immune response against pathogens is crucial to avoid excessive responses that may be harmful to the host. In several primary immunodeficiencies, weak responses against pathogens co-exist with autoimmunity indicating a global loss of regulation. This is the case of the Wiskott-Aldrich syndrome, an immunodeficiency caused by mutations in a key regulator of the actin cytoskeleton that lead to aberrant intracellular and extracellular trafficking of immune cells.

The study, funded by the Telethon Foundation, is the result of a joint effort between Francesca Prete and Mayrel Labrada at ICGEB, and researchers in the Group of Anna Villa at the San Raffaele Hospital in Milan, together with extensive collaboration with numerous, renowned, international centres for the study of primary immunodeficiencies.

Related article:

Trieste City of Knowledge: Wiskott-Aldrich syndrome investigated

Published in the February 11 issue of JEM and online from Monday, January 21 2013

Prete, F., Catucci, M., Labrada, M., Gobessi, S., Carmina Castiell, M., Metin, A., Hambleton, S., Bredius, R., Notarangelo, L.D., van der Burg, M., Kalinke, U., Villa, A., Benvenuti, F. 2013. Wiskott-Aldrich syndrome protein-mediated actin dynamics control type-I interferon production in plasmacytoid dendritic cells. J Exp Med doi: 10.1084/jem.20120363

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Altered endocytic trafficking and handling of antigens in Wiskott-Aldrich syndrome protein deficient plasmacytoid DCs leads to exaggerated production of type-I interferon and development of autoimmunity. Micrographs show cells with internalized fluorescent agonist of TLR9 (CpG-A in green) and counterstained with markers of early endosomes (EEA-1 in red). Quantification of early endosomes (EE) and CpG-A volumes and colocalization index were quantified on reconstructed z-sections using the Volocity software.

 

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Federica Benvenuti (front) and her team at the Cellular Immunology Lab, ICGEB Trieste, Italy

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