HDAC6 Deletion Decreases Pristane-induced Inflammation

Area of Science:

• Immunology
• Molecular Biology
• Autoimmune Diseases

Background:

• Systemic lupus erythematosus (SLE) involves excessive inflammation and autoantibodies.
• Histone deacetylase 6 (HDAC6) inhibition shows potential in reducing lupus inflammation.
• HDAC6-/- mice and a selective inhibitor (ACY-738) were used to investigate HDAC6's role.

Purpose of the Study:

• To investigate the role of HDAC6 in pristane-induced lupus model.
• To determine the effect of HDAC6 deficiency on inflammatory cell populations and IFN signature genes.
• To explore the in vitro effects of HDAC6 inhibition on inflammatory signaling pathways.

Main Methods:

• Pristane or PBS was administered to wild-type (WT) and HDAC6-/- mice.
• Spleen and body weights were measured; sera and cells were collected for flow cytometry.
• RT-qPCR was used to analyze IFN signature genes; in vitro studies used J774A.1 cells.

Main Results:

• Pristane increased spleen weight and inflammatory monocytes/neutrophils, which were reduced in HDAC6-/- mice.
• HDAC6 deficiency increased CD69+ T and B cells but did not affect IFN signature genes.
• In vitro, HDAC6 inhibition increased NF-κB acetylation and Stat1 phosphorylation, leading to iNOS production.

Conclusions:

• HDAC6 deficiency partially ameliorates lupus inflammation by reducing inflammatory monocytes and neutrophils.
• HDAC6 plays a complex role, with inhibition affecting some inflammatory pathways but not others, including IFN responses.
• Further research is needed to fully elucidate HDAC6's therapeutic potential in SLE.