Wiskott-Aldrich Syndrome at the nexus of autoimmune and primary immunodeficiency diseases.

FEBS Lett

Immunoregulation Section, Autoimmunity Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Published: December 2011

AI Article Synopsis

  • Wiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency marked by high rates of autoimmunity due to mutations in the Wiskott-Aldrich Syndrome protein (WASp).
  • WASp is crucial for linking cell surface receptor signaling to actin polymerization, affecting various immune cell functions and contributing to immune tolerance via regulatory mechanisms.
  • The syndrome presents unique immune defects, making it a valuable model for understanding complex immune diseases influenced by both genetic and environmental factors.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580218PMC
http://dx.doi.org/10.1016/j.febslet.2011.10.031DOI Listing

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