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Wiskott–Aldrich Syndrome at the nexus of autoimmune and primary immunodeficiency diseases
Author(s) -
Cleland Sophia Y.,
Siegel Richard M.
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.10.031
Subject(s) - primary immunodeficiency , wiskott–aldrich syndrome , nexus (standard) , immunodeficiency , immunology , wiskott–aldrich syndrome protein , medicine , virology , biology , genetics , immune system , gene , computer science , actin cytoskeleton , cytoskeleton , cell , embedded system
Wiskott–Aldrich Syndrome (WAS) is a X‐linked primary immunodeficiency disorder also marked by a very high (up to 70%) incidence of autoimmunity. Wiskott–Aldrich Syndrome arises from mutations in the Wiskott–Aldrich Syndrome protein (WASp), a cytoplasmic protein that links signaling by cell surface receptors such as the T‐cell receptor and integrins to actin polymerization. WASp promotes the functions of multiple cell types that support immune responses, but also is important for the function of regulatory T cells and in TCR‐induced apoptosis, two negative mechanisms of immune regulation that maintain peripheral immune tolerance. Here we review the nature of immune defects and autoimmunity in WAS and WASp deficient mice and discuss how this single gene defect can simultaneously impair immune responses to pathogens and promote autoimmunity. The myriad cellular immune defects found in WAS make this Mendelian syndrome an interesting model for the study of more complex immune diseases that arise from the interplay of environmental and multiple genetic risk factors.