Intrinsic dendritic cell abnormalities in Wiskott-Aldrich syndrome

作者：Michael Binks, Gareth Elwyn Jones, Paul M. Brickell, Christine Kinnon, David R. Katz, Adrian James Thrasher · 发表于：European Journal of Immunology · 年份：1998 · DOI：10.1002/(sici)1521-4141(199810)28:10<3259::aid-immu3259>3.0.co;2-b · 被引用次数：116 · 研究领域：Cell Adhesion Molecules Research、Cellular Mechanics and Interactions、Immunotherapy and Immune Responses

Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by immune deficiency, eczema, and microthrombocytopenia. Biochemical evidence indicates that the Wiskott-Aldrich syndrome protein (WASp) is involved in regulating the actin cytoskeleton. Here we report that WAS dendritic cells (DC) have an immunophenotype very similar to normal DC. However, as a consequence of an intrinsically abnormal cytoarchitecture, they are unable to polarize normally and have severely reduced translocational motility in vitro. These findings indicate that WASp is an essential effector for Cdc-42-mediated polarization of primary hematopoietic cells, and suggest that a significant component of the clinical phenotype of WAS could arise from peripheral DC dysmotility and aberrant immune cell trafficking in vivo. Intrinsic dysfunction of the DC population may also have an important role in the pathogenesis of other primary immunodeficiency syndromes, while induced changes in DC cytoskeletal signaling pathways may contribute to the initiation of acquired immunological and inflammatory disorders.