Journal article
Manipulation of B-cell responses with histone deacetylase inhibitors
M Waibel, AJ Christiansen, ML Hibbs, J Shortt, SA Jones, I Simpson, A Light, K O'Donnell, EF Morand, DM Tarlinton, RW Johnstone, ED Hawkins
Nature Communications | Published : 2015
DOI: 10.1038/ncomms7838
Abstract
Histone deacetylase inhibitors (HDACi) are approved for treating certain haematological malignancies, however, recent evidence also illustrates they are modulators of the immune system. In experimental models, HDACi are particularly potent against malignancies originating from the B-lymphocyte lineage. Here we examine the ability of this class of compounds to modify both protective and autoimmune antibody responses. In vitro, HDACi affect B-cell proliferation, survival and differentiation in an HDAC-class-dependent manner. Strikingly, treatment of lupus-prone Mrl/lpr mice with the HDACi panobinostat significantly reduces autoreactive plasma-cell numbers, autoantibodies and nephritis, while o..
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Funding Acknowledgements
The work was funded by the Australian National Health and Medical Research Council (NHMRC). M.L.H. and E.D.H. were supported by fellowships from the NHMRC. A.J.C. was supported by fellowships from the NHMRC and Cancer Council Victoria. R.W.J. was supported by an NHMRC Principal Research Fellowship, project and program grants from the NHMRC, the Cancer Council Victoria, The Leukaemia Foundation of Australia and the Victorian Cancer Agency (VCA). J.S. was supported by a VCA/Snowdome Foundation 'Eva & Les Erdi' Fellowship. D.M.T. was supported by grants and a fellowship from the NHMRC. M.W. was supported by a fellowship from the Deutsche Forschungsgemeinschaft and funding from the NHMRC. E.F.M. was supported by project and development grants from the NHMRC. S.A.J. was supported by a fellowship from Arthritis Australia. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. We also thank Dr Peter Atadja for providing Panobinostat and for helpful discussions. E.D.H. thanks Sarah Russell for mentorship through the project. We thank Richard Tothill for scientific input on the project and Professor Joe Trapani for comments on the manuscript. We thank Michael Durrant for animal husbandry as well as Kelly Ramsbottom and Ben Martin for technical contributions. We also thank Steve Asquith for additional help with histology.