INTRODUCTION

Psoriasis is a complex autoimmune inflammatory disease that occurs in genetically susceptible

individuals and presents with the development of inflammatory plaques on the skin (picture 1A-B).
Although early concepts of the pathogenesis of psoriasis focused primarily on keratinocyte
hyperproliferation, dysregulation of the immune system is now recognized as a critical event in this
disease. The evolving knowledge of the role of the immune system in psoriasis has had a significant
impact on treatment development. Many new and emerging therapeutic agents target specific
immunologic aspects of psoriatic disease. (See"Treatment of psoriasis".)
The pathophysiology of psoriasis will be discussed here. The epidemiology, genetics, clinical features,
diagnosis, and management of psoriasis are reviewed separately. (See "Epidemiology, clinical
manifestations, and diagnosis of psoriasis" and"Treatment selection for moderate to severe plaque
psoriasis in special populations".)
OVERVIEW
Involvement of the immune system in psoriasis was first indicated in early studies that identified complex
infiltrates of leukocytes involved in both innate and adaptive immunity in psoriatic skin [1,2]. Subsequent
studies have supported the concept that interactions between dendritic cells, T cells, keratinocytes,
neutrophils, and the cytokines released from immune cells likely contribute to the initiation and
perpetuation of the cutaneous inflammation that is characteristic of psoriasis [3]. A basic sequence of the
immunologic events that are theorized to occur in psoriasis is described below [3]:
Antigenic stimuli contribute to the activation of plasmacytoid dendritic cells and other innate
immune cells in the skin.
Proinflammatory cytokines produced by innate immune cells, including interferon (IFN)-alpha,
stimulate the activation of myeloid dendritic cells in the skin.
Myeloid dendritic cells produce cytokines, such as interleukin (IL)-23 and IL-12 that stimulate the
attraction, activation, and differentiation of T cells.
Recruited T cells produce cytokines that stimulate keratinocytes to proliferate and produce
proinflammatory antimicrobial peptides and cytokines.
Cytokines produced by immune cells and keratinocytes perpetuate the inflammatory process via
participation in positive feedback loops.
The specific components of this pathway are reviewed below.