Current Concepts of Psoriasis Immunopathogenesis

Abstract

Psoriasis is a recurrent, chronic, immune-mediated, systemic inflammatory disease of the skin, joints, and other organic systems. After atopic dermatitis, chronic stationary psoriasis is the most common inflammatory skin disease, affecting an average of 2-4% of the world's population. The disease carries a significant burden due to its numerous comorbidities and the major impact on patients' social and emotional aspects of life. According to current knowledge, psoriasis is a multifactorial disease that occurs in genetically predisposed individuals under various environmental factors, which trigger an immune response disorder with a series of complex inflammatory cascades. The disease is initiated and maintained by mutual interaction of the innate and adaptive immune cells, primarily dendritic cells, T lymphocytes, and keratinocytes, whose leading role alternates at different stages of the disease, consisting mainly in the IL-23/Th17 pathway. Inflammatory events result in consequent epidermal and dermal changes and evolution of the characteristic psoriatic phenotype, respectively. This paper aims to present a comprehensive overview of current knowledge on psoriasis genetic and environmental etiological factors, immunopathogenesis, and the leading cellular and cytokine participants in the inflammatory pathways of this disease.

Keywords: IL-23/Th17 pathway; NK cells; NKT cells; T lymphocytes; dendritic cells; etiology; immunopathogenesis; keratinocytes; macrophages; psoriasis.

Figure 1

Major effector cells and signaling pathways in the immunopathogenesis of psoriasis. The immunopathogenesis of psoriasis involves a complex inflammatory cascade, which is initially triggered by innate immune cells (keratinocytes, dendritic cells, NKT cells, macrophages). At the same time, the disease progresses and is maintained by their interaction with adaptive immune cells (T lymphocytes). The central mechanism of the disease is the IL-23/Th17 axis, whose executive cytokines IL-22 and IL-17A/F lead to keratinocyte proliferation, production of proinflammatory cytokines, chemokines and AMP, and the formation of a positive feedback loop, which maintains the inflammatory process. Cytokines in cells activate signaling and transcription pathways (cAMP, JAK-STAT), which achieve increased transcription of messenger genes and cytokines involved in the disease pathogenesis. Adapted from: [36].