Journal article

Bcl-2 antagonists kill plasmacytoid dendritic cells from lupus-prone mice and dampen interferon-α production

Y Zhan, EM Carrington, HJ Ko, IB Vikstrom, S Oon, JG Zhang, D Vremec, JL Brady, P Bouillet, L Wu, DCS Huang, IP Wicks, EF Morand, A Strasser, AM Lew

Arthritis and Rheumatology | Published : 2015

Abstract

Objective Interferon-α (IFNα)-producing plasmacytoid dendritic cells (PDCs) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). IFNα-related genes are highlighted among SLE susceptibility alleles and are characteristically expressed in the blood of patients with SLE, while in mouse models of lupus, PDC numbers and IFNα production are increased. This study was undertaken to investigate the effects of inhibitors that selectively target different antiapoptotic molecules on the survival of PDCs. Methods PDC numbers, in vitro survival, and expression of antiapoptotic molecules were evaluated in lupus-prone (NZB × NZW)F1 (NZB/NZW) mice. The impact of Bcl-2 antagonists and glu..

View full abstract

Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia program


Awarded by Leukemia & Lymphoma Society Special Center of Research


Awarded by NHMRC Independent Research Institutes Infrastructure Support Scheme



Funding Acknowledgements

Supported by National Health and Medical Research Council (NHMRC) of Australia program grants (1016647 to Drs. Zhang and Wicks, 1016701 to Drs. Huang and Strasser, and 1037321 to Dr. Lew), project grants (637324 and 1007703 to Dr. Zhan, 1021374 to Dr. Vikstrom, 104610 to Dr. Strasser, and 1043414 to Dr. Lew), and fellowships (1043149 to Dr. Huang and 1020363 to Dr. Strasser), and by the Juvenile Diabetes Research Foundation, the Rebecca L. Cooper Foundation, the Leukemia & Lymphoma Society Special Center of Research (grant 7001-13 to Drs. Huang and Strasser), NHMRC Independent Research Institutes Infrastructure Support Scheme grant 361646, Victorian State Government Operational Infrastructure Support, and the Australian Government.