Bouma, G;
Carter, NA;
Recher, M;
Malinova, D;
Adriani, M;
Notarangelo, LD;
Burns, SO;
... Thrasher, AJ; + view all
(2014)
Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: modulatory role of regulatory B cells.
Eur J Immunol
, 44
(9)
2692 - 2702.
10.1002/eji.201344245.
![[thumbnail of eji3049.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/application_pdf.png) |
PDF
eji3049.pdf Download (1MB) |
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.
| Type: | Article |
|---|---|
| Title: | Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: modulatory role of regulatory B cells. |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/eji.201344245 |
| Publisher version: | http://dx.doi.org/10.1002/eji.201344245 |
| Language: | English |
| Additional information: | © 2014 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Arthritis, Immune regulation, Regulatory B cells, Regulatory T cell, Th17 cells, Wiskott-Aldrich syndrome protein, Animals, Arthritis, Experimental, Autoimmune Diseases, B-Lymphocyte Subsets, Female, Humans, Interleukin-10, Male, Mice, Mice, Knockout, T-Lymphocytes, Regulatory, Th17 Cells, Wiskott-Aldrich Syndrome Protein |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1433361 |
Archive Staff Only
 |
View Item |
