Psoriasis is a chronic autoimmune disease characterized by excess inflammation of skin cells called keratinocytes, resulting in itching, burning, and stinging sensations of the skin.  Excess inflammation of keratinocytes is mediated through the overproduction of immune-signaling molecules called cytokines, which serve to regulate the inflammatory response of the skin by altering psoriasis-related gene expression.

While a complete understanding of disease progression remains elusive, a specific pro-inflammatory cytokine, Interleukin-17A (IL-17A), has been implicated as a key contributor to the inflammation during psoriasis. While important, these results were obtained through clinical studies and did not provide information about the biology governing IL-17A-dependent activation of the keratinocyte inflammatory response during psoriasis.

A recent study from Hokkaido University in Japan titled “Understanding the underlying mechanisms that lead to psoriasis,” published in the Journal of International Immunology, aims to explain the precise mechanism by which cytokines, particularly IL-17A, contribute to excess inflammation of keratinocyte skin cells.

By growing keratinocytes in a single layer, scientists successfully generated a laboratory model of psoriasis that reproduced the previous clinical findings of cytokine-dependent activation of psoriasis-related genes. Using this model, the inflammatory-specific gene expression of keratinocytes was measured both with and without the addition of cytokines.

Initially, keratinocytes were exposed to a cocktail of six cytokines, including IL-17A, and psoriasis-related gene expression was examined. To determine the particular impact of each of the cytokines in the cocktail, scientists removed each cytokine singly. If the removal of a cytokine resulted in failure of the cocktail to induce psoriasis-related gene expression, it indicated that particular cytokine was important for the pro-inflammatory response of keratinocytes during psoriasis.

This study revealed that IL-17A does indeed play a critical role in the activation of inflammatory gene expression during psoriasis. The laboratory model of psoriasis validated in this study offers a controlled method by which to determine the exact psoriasis-related gene expression profile of keratinocytes.

This information will likely further researchers’ understanding of psoriasis and uncover key contributors of disease progression, some of which may be potential drug targets in the future.