Increased Sensitivity to Interferon-α in Psoriatic T Cells

Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-α plays an important role in host defense against infections, but recent data have also implicated IFN-α in psoriasis. Thus, IFN-α induces or aggravates psoriasis in some patients, and mice lacking a transcriptional attenuator of IFN-α/β signaling spontaneously develop a psoriasis-like inflammatory skin disease characterized by CD8+-infiltrating T cells. In this study, we therefore investigate IFN-α signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-α, on the level of signal transducers and activators of transcription (STAT) activation, compared with infiltrating T cells from skin of non-psoriatic donors. Functionally, the increased IFN-α signaling leads to an increased binding of STAT4 to the IFN-γ promotor, IFN-γ production, and inhibition of T cell growth. In contrast, to STAT responses to other cytokines were not changed in psoriasis. In conclusion, we provide evidence that psoriatic T cells have an increased sensitivity to IFN-α. Thus, our data suggest that increased IFN-α signaling is involved in the pathogenesis of psoriasis.