The biological basis of disease recurrence in psoriasis: a historical perspective and current models.

Abstract

SummaryA key challenge in psoriasis therapy is the tendency for lesions to recur in previously affected anatomical locations after treatment discontinuation following lesion resolution. Available evidence supports the concept of a localized immunological ‘memory’ that persists in resolved skin after complete disappearance of visible inflammation, as well as the role of a specific subpopulation of T cells characterized by the dermotropic CCR4+ phenotype and forming a local memory. Increasing knowledge of the interleukin (IL)‐23/T helper 17 (Th17) cell pathway in psoriasis immunopathology is pointing away from the historical classification of psoriasis as primarily a Th1‐type disease. Research undertaken from the 1990s to the mid‐2000s provided evidence for the existence of a large population of CD8+ and CD4+ tissue‐resident memory T cells in resolved skin, which can initiate and perpetuate immune responses of psoriasis in the absence of T‐cell recruitment from the blood. Dendritic cells (DCs) are antigen‐presenting cells that contribute to psoriasis pathology via the secretion of IL‐23, the upstream regulator of Th17 cells, while plasmacytoid DCs are involved via IL‐36 signalling and type I interferon activation. Overall, the evidence discussed in this review indicates that IL‐23‐driven/IL‐17‐producing T cells play a critical role in psoriasis pathology and recurrence, making these cytokines logical therapeutic targets. The review also explains the clinical efficacy of IL‐17 and IL‐23 receptor blockers in the treatment of psoriasis.