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 other immune parameters remain largely unaffected. Immunized control mice treated with panobinostat or the clinically approved HDACi vorinostat have significantly impaired primary antibody responses, but these treatments surprisingly spare circulating memory B cells. These studies indicate that panobinostat is a potential therapy for B-cell-driven autoimmune conditions and HDACi do not induce major long-term detrimental effects on B-cell memory.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Waibel M,Christiansen AJ,Hibbs ML,Shortt J,Jones SA,Simpson I,Light A,O'Donnell K,Morand EF,Tarlinton DM,Johnstone RW,Hawkins EDdoi
10.1038/ncomms7838subject
Has Abstractpub_date
2015-04-27 00:00:00pages
6838issn
2041-1723pii
ncomms7838journal_volume
6pub_type
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