The
COVID-19 pandemic has had a devastating impact worldwide and has been a great challenge for the scientific community.
Vaccines against SARS-CoV-2 are now efficiently lessening
COVID-19 mortality, although finding a cure for this
infection is still a priority. An unbalanced immune response and the uncontrolled release of proinflammatory
cytokines are features of
COVID-19 pathophysiology and contribute to
disease progression and worsening.
Histone deacetylases (HDACs) have gained interest in immunology, as they regulate the innate and adaptative immune response at different levels. Inhibitors of these
enzymes have already proven therapeutic potential in
cancer and are currently being investigated for the treatment of
autoimmune diseases. We thus tested the effects of different
HDAC inhibitors, with a focus on a selective HDAC6 inhibitor, on immune and epithelial cells in in vitro models that mimic cells activation after
viral infection. Our data indicate that
HDAC inhibitors reduce
cytokines release by airway epithelial cells, monocytes and macrophages. This anti-inflammatory effect occurs together with the reduction of monocytes activation and T cell exhaustion and with an increase of T cell differentiation towards a T central memory phenotype. Moreover,
HDAC inhibitors hinder IFN-I expression and downstream effects in both airway epithelial cells and immune cells, thus potentially counteracting the negative effects promoted in critical
COVID-19 patients by the late or persistent IFN-I pathway activation. All these data suggest that an epigenetic therapeutic approach based on
HDAC inhibitors represents a promising pharmacological treatment for severe
COVID-19 patients.