Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: modulatory role of regulatory B cells.
Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: modulatory role of regulatory B cells.
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DOI：
10.1002/eji.201344245
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发表时间：
2014-09
影响因子：
5.4
通讯作者：
Thrasher, Adrian J.
中科院分区：
文献类型：
--
作者：
Bouma, Gerben;Carter, Natalie A.;Recher, Mike;Malinova, Dessislava;Adriani, Marsilio;Notarangelo, Luigi D.;Burns, Siobhan O.;Mauri, Claudia;Thrasher, Adrian J.
关键词：
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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DOI：
10.4049/jimmunol.0803052
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Blair PA;Chavez-Rueda KA;Evans JG;Shlomchik MJ;Eddaoudi A;Isenberg DA;Ehrenstein MR;Mauri C
通讯作者：
Mauri C
影响因子：
15.9
作者：
Matsushita, Takashi;Yanaba, Koichi;Tedder, Thomas F.
通讯作者：
Tedder, Thomas F.
影响因子：
32.4
作者：
Mizoguchi, A;Mizoguchi, E;Bhan, AK
通讯作者：
Bhan, AK
影响因子：
8.6
作者：
Adriani, Marsilio;Aoki, Joseph;Schwartzberg, Pamela L.
通讯作者：
Schwartzberg, Pamela L.
影响因子：
20.3
作者：
Bouma, Gerben;Burns, Siobhan;Thrasher, Adrian J.
通讯作者：
Thrasher, Adrian J.