Reference : Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis
Scientific journals : Article
Human health sciences : Hematology
Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis
Humblet, Stéphanie mailto [Université de Liège - ULiège > > GIGA-R : Hématologie >]
Sather, B. [ > > ]
Anover, S. [ > > ]
Becker-Herman, S. [ > > ]
Kasprowicz, D. J. [ > > ]
Khim, S. [ > > ]
Nguyen, T. [ > > ]
Hudkins-Loya, K. [ > > ]
Alpers, C. E. [ > > ]
Ziegler, S. F. [ > > ]
Ochs, H. [ > > ]
Torgerson, T. [ > > ]
Campbell, D. J. [ > > ]
Rawlings, D. J. [ > > ]
Journal of Clinical Investigation
American Society for Clinical Investigation
Yes (verified by ORBi)
Ann Arbor
[en] 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 paradoxial observations. While WASp-deficient (WASp-/-) mice exibited 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 autoimmune pathology in Foxp3-/- Scurfy (sf) mice. Finally, WASp+ Treg 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.

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