Apremilast increases IL-10-producing regulatory B cells and decreases proinflammatory T cells and innate cells in psoriatic arthritis and psoriasis.

Abstract

Psoriatic arthritis (PsA) and psoriasis are immune-mediated inflammatory diseases sharing common immunological mechanisms. Regulatory B cells (Breg cells) producing IL-10 (B10 cells), a critical anti-inflammatory B-cell subset, were found to be decreased in both PsA and psoriasis. Apremilast, a phosphodiesterase-4(PDE4) inhibitor, increases IL-10 and therefore, we examined the effect of apremilast on Breg cells. Fifty patients, including 20 with PsA and 30 with psoriasis, were included in the study. The effect of apremilast on Breg cells at 3, 6 and 12 months post-treatment, was examined by flow cytometry in ODN2006 (TLR9)-stimulated peripheral blood mononuclear cells and magnetically-isolated cells. Th1 cells, Th17 cells and NKT were also measured. Ex vivo stimulated cell analysis identified that post-apremilast (IL-10+CD19+) B10 cells were increased in all PsA and psoriasis patients and correlated with psoriatic skin and joint clinical improvement. Apremilast decreased IFNγ(+) T and NKT cells and IL-17(+)NKT cells. B10 cells also inversely correlated with Th1 cells, and IFNγ(+)NKT cells. These results suggest that Breg cells are a major target of apremilast in PsA and psoriasis and that apremilast-induced increase of Breg cells is associated with a decrease of Th1 cells, IFNγ-producing NKT cells and IL-17-producing NKT cells.