Chapter 2 Pathogenesis of psoriasis and psoriatic arthritis

Pathophysiology of psoriasis The pathophysiology of psoriasis is multifaceted and dynamic, involving a complex interplay between constitutive cells of the skin and the innate and adaptive immune systems. Until the early 1980s, psoriasis was considered to be primarily a disease of epidermal keratinocyte proliferation, with the cutaneous inflammatory infiltrate a secondary consequence [1]. However, the effective use of therapies designed to inhibit T-cell activation, such as cyclosporine [2] in the late 1970s, and interleukin (IL)-2 toxin [3] and alefacept [4,5] (lymphocyte function-associated antigen3Ig) and IL-17A [6] more latterly, has led to a paradigm shift in psoriasis pathogenesis to an immune cell-mediated inflammatory etiology. Over the past decade, evidence from mouse models and translational research strongly indicates that psoriatic plaques result from both a primary defect in keratinocytes and an inappropriate innate and adaptive immune response mediated mainly by resident and infiltrating T cells [7–10]. Psoriatic skin lesions are highly infiltrated most notably with CD3+ T lymphocytes, CD4+ T helper cells and CD11c+ myeloid dendritic cells within the dermis [11,12], and CD8+ T cells and neutrophils in the epidermis [13]. Complex interactions between these T cells,