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Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: Modulatory role of regulatory B cells

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Bouma Gerben, Carter Natalie A., Recher Mike, Malinova Dessislava, Adriani Marsilio, Notarangelo Luigi D., Burns Siobhan O., Mauri Claudia, Thrasher Adrian J.,
Project Analysis of RAG-dependent immunodeficiency and autoimmunity
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Original article (peer-reviewed)

Journal EUROPEAN JOURNAL OF IMMUNOLOGY
Volume (Issue) 44(9)
Page(s) 2692 - 2702
Title of proceedings EUROPEAN JOURNAL OF IMMUNOLOGY
DOI 10.1002/eji.201344245

Abstract

Patients deficient in the cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASp) are predisposed to varied autoimmunity, suggesting it has an important controlling role in participating cells. IL-10-producing regulatory B (Breg) cells are emerging as important mediators of immunosuppressive activity. In experimental, antigen-induced arthritis WASp-deficient (WASp knockout [WAS KO]) mice developed exacerbated disease associated with decreased Breg cells and regulatory T (Treg) cells, but increased Th17 cells in knee-draining LNs. Arthritic WAS KO mice showed increased serum levels of B-cell-activating factor, while their B cells were unresponsive in terms of B-cell-activating factor induced survival and IL-10 production. Adoptive transfer of WT Breg cells ameliorated arthritis in WAS KO recipients and restored a normal balance of Treg and Th17 cells. Mice with B-cell-restricted WASp deficiency, however, did not develop exacerbated arthritis, despite exhibiting reduced Breg- and Treg-cell numbers during active disease, and Th17 cells were not increased over equivalent WT levels. These findings support a contributory role for defective Breg cells in the development of WAS-related autoimmunity, but demonstrate that functional competence in other regulatory populations can be compensatory. A properly regulated cytoskeleton is therefore important for normal Breg-cell activity and complementation of defects in this lineage is likely to have important therapeutic benefits.
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