No abstract

Psoriasis and atherosclerosis are diseases in which effector T lymphocytes such as Helper T cells type 1 (Th1) and 17 (Th17) play integral roles in disease pathogenesis and progression. Regulatory T cells (Treg) also exert clinically important anti-inflammatory effects that are pathologically altered in psoriasis and atherosclerosis. We review the immunological pathways involving Th1, Th17 and Treg cells that are common to psoriasis and atherosclerosis. These shared pathways provide the basis for mechanisms that may explain the epidemiologic observation that patients with psoriasis have an increased risk of heart disease. Improved understanding of these pathways will guide future experiments and may lead to the development of therapeutics that prevent or treat cardiovascular complications in patients with psoriasis.

Recent studies suggest that cigarette smoking may trigger the development of psoriasis through oxidative, inflammatory and genetic mechanisms. Smoking initiates formation of free radicals that stimulate cell signalling pathways active in psoriasis including mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK-STAT). Smoking damages the skin by increasing formation of reactive oxygen species and decreasing the gene expression of antioxidants. Nicotine also stimulates innate immune cells integral to the pathogenesis of psoriasis including dendritic cells, macrophages and keratinocytes. These cells release cytokines that activate T lymphocytes and perpetuate a cycle of chronic inflammation. Smoking also enhances expression of genes known to confer an increased risk of psoriasis, including HLA-Cw6, HLA-DQA1*0201 and CYP1A1. Improved understanding of the possible link between smoking and psoriasis pathogenesis may provide further insight into mechanisms underlying smoking, psoriasis and risk of subsequent cardiovascular disease.