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Title: Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis
Authors: Humblet-Baron, Stephanie ×
Sather, Blythe
Anover, Stephanie
Becker-Herman, Shirly
Kasprowicz, Debora J
Khim, Socheath
Nguyen, Thuc
Hudkins-Loya, Kelly
Alpers, Charles E
Ziegler, Steve F
Ochs, Hans
Torgerson, Troy
Campbell, Daniel J
Rawlings, David J #
Issue Date: Feb-2007
Publisher: American Society for Clinical Investigation
Series Title: Journal of Clinical Investigation vol:117 issue:2 pages:407-418
Abstract: Wiskott-Aldrich syndrome protein (WASP) is essential for optimal T cell activation. Patients with WAS exhibit both immunodeficiency and a marked susceptibility to systemic autoimmunity. We investigated whether alterations in Treg function might explain these paradoxical observations. While WASp-deficient (WASP(-/-)) mice exhibited normal thymic Treg generation, the competitive fitness of peripheral Tregs was severely compromised. The total percentage of forkhead box P3-positive (Foxp3(+)) Tregs among CD4(+)T cells was reduced, and WASP-/- Tregs were rapidly outcompeted by WASp(+) Tregs in vivo. These findings correlated with reduced expression of markers associated with self-antigen-driven peripheral Treg activation and homing to inflamed tissue. Consistent with these findings, WASP-/- Tregs showed a reduced ability to control aberrant T cell activation and autoinimune pathology in Foxp3(-/-) Scurfy (sf) mice. Finally, WASp(+) Tregs exhibited a marked selective advantage in vivo in a WAS patient with a spontaneous revertant mutation, indicating that altered Treg fitness likely explains the autoimmune features in human WAS.
URI: 
ISSN: 0021-9738
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Genetics of Autoimmunity
× corresponding author
# (joint) last author

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