Human β-defensin-2 enhances IFN-γ and IL-10 production and suppresses IL-17 production in T cells.

Psoriasis is an inflammatory dermatosis with enhanced expression of hBD-2 in keratinocytes and infiltration of cytokine-producing T cells, which in turn, up- or down-regulate hBD-2 expression. We determined the serum levels of hBD-2 and cytokines in psoriasis patients and analyzed the effects of hBD-2 on cytokine production in human peripheral blood T cells. Serum hBD-2 levels in patients were higher than those in controls and correlated with PASI, serum IFN-γ, and IL-10 levels and correlated inversely with serum IL-17 levels. IFN-γ, IL-17, IL-22, TNF-α, IL-1β, and IL-6 enhanced, and IL-10, IL-4, and IL-13 suppressed hBD-2 secretion from keratinocytes. hBD-2 enhanced secretion and mRNA levels of IFN-γ, TNF-α, IL-10, IL-1β, IL-6, and IL-22 and reduced those of IL-17 in CD3/28-stimulated T cells. These effects of hBD-2 were counteracted by PTX. hBD-2 induced phosphorylation of JNK, ERK, and Akt in T cells. Inhibitors of these signals attenuated hBD-2-induced production of IFN-γ, TNF-α, IL-10, IL-1β, IL-6, and IL-22. hBD-2 suppressed phosphorylation of STAT3 and enhanced expression of SOCS3 in CD3/28-stimulated T cells. siRNA against SOCS3 reversed hBD-2-induced suppression of IL-17 production and STAT3 phosphorylation. JNK and MEK inhibitors suppressed hBD-2-induced expression of SOCS3. In conclusion, hBD-2 may bind PTX-sensitive GPCR(s) on T cells and act as a stimulator by enhancing IFN-γ, TNF-α, IL-1β, IL-6, and IL-22 production via JNK, MEK/ERK, and PI3K/Akt and as a regulator by suppressing IL-17 production via SOCS3 or by stimulating IL-10 production.