What causes keratinocytes to proliferate in Psoriasis?

By SWA

Psoriasis is a chronic autoimmune condition characterized by the rapid proliferation of keratinocytes in the epidermis, leading to the development of thick, scaly plaques on the skin. 

The stratum corneum is the outermost layer of the epidermis and marks the final stage of keratinocyte maturation and development. Keratinocytes at the basal layer of the epidermis are proliferative, and as the cells mature up the epidermis, they slowly lose proliferative potential and undergo programmed destruction.

The proliferation of keratinocytes in psoriasis, particularly in the basal layer of the epidermis, and their altered maturation process are driven by a complex interplay of genetic, immunological, and environmental factors. Here are some key factors contributing to this process:

  1. Immune System Dysregulation: One of the primary causes of keratinocyte hyperproliferation in psoriasis is an abnormal immune response. In psoriasis, T cells are activated abnormally, which leads to the production of various cytokines (such as tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), interleukin-22 (IL-22), and interleukin-23 (IL-23)). These cytokines stimulate keratinocytes to proliferate more rapidly than normal and also affect their differentiation process.

  2. Genetic Susceptibility: Psoriasis has a strong genetic component, with multiple genes implicated in its pathogenesis. These genes are often involved in the regulation of the immune system and skin barrier function. Genetic predisposition can influence the response of keratinocytes to environmental triggers and immune signals, leading to their abnormal proliferation.

  3. Environmental Triggers: Various environmental factors can trigger or exacerbate psoriasis in individuals with a genetic predisposition. These include stress, skin injury (the Koebner phenomenon), certain medications, and infections. These triggers can initiate or worsen the immune dysregulation that leads to keratinocyte hyperproliferation.

  4. Disrupted Skin Barrier: The rapid turnover and altered differentiation of keratinocytes in psoriasis lead to changes in the skin barrier, making it less effective in protecting against external insults and more prone to inflammation and damage. This disrupted barrier can further perpetuate the cycle of inflammation and keratinocyte proliferation.

  5. Cytokine-Driven Growth: The cytokines produced by activated immune cells not only cause inflammation but also directly act on keratinocytes to stimulate their growth and inhibit their programmed cell death. This leads to an accumulation of immature skin cells and the formation of psoriatic plaques.

In psoriasis, the normal process of keratinocyte proliferation and programmed cell death is significantly accelerated and dysregulated, leading to the characteristic symptoms of the condition. Treatments for psoriasis often aim to reduce inflammation, slow down keratinocyte proliferation, and normalize skin cell maturation.


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