Koebner phenomenon leading to the formation of new psoriatic lesions: evidences and mechanisms

Abstract

Koebner phenomenon refers to the emergence of new psoriatic lesions in the healthy skin regions following an injury/trauma to psoriatic patients. The occurrence of psoriatic lesions at unusual areas of the body regions such as on penis, around eyes and on keloids suggest that the Koebner phenomenon may be responsible for these lesions. A number of agents/triggers have been reported to induce the development of new psoriatic lesions in healthy skin areas and these include, tattooing skin, radiations, skin incision, viral infections and striae etc. The different mechanisms that contribute in inducing the development of new psoriatic lesions as Koebernization include the involvement of mast cell-derived inflammatory mediators such as tryptase, IL-6, IL-8, IL-17, and IL-36γ. Moreover, an increased expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) also contribute in Koebernization. Apart from these, there is a critical role of α 2 β1 integrins, S100A7 (psoriasin) and S100A15 (koebnerisin), change in the ratio of CD4+/CD8+ T cells, down-regulation of mechanosensitive polycystin 1 protein, decrease in inflammation controlling atypical chemokine receptor 2 (ACKR2), reduced expression of N-methyl-d-aspartate (NMDA) receptors (NMDARs) on the keratinocytes and increase in levels of chemokines (CXCL8 and CCL20) in inducing formation of new psoriatic lesions. The present review discusses the role of Koebner phenomenon in the development of new psoriatic lesions. Moreover, it also describes the mechanisms involved in Koebernization in the form of discussion of different key targets that may be potentially modulated pharmacologically to attenuate/halt the development of new psoriatic lesions.

Keywords: Koebner phenomenon; cytokines; immune system; psoriasis; tryptase.

Figure 1. Representation of the role of mast cells-derived mediators in inducing the formation of new psoriatic lesions

Tryptase may directly act as a mitogen to increase the proliferation of epithelial cells and dermal fibroblasts. Moreover, tryptase may activate PAR-2 receptors located on the mast cells to induce its activation, thus leading to the initiation of the self-amplification process. In response, the activated mast cells release IL-8, which contributes to the inflammatory process. The psoriatic keratinocytes act in concert with the mast cells to potentiate the inflammation in different ways including the release of IL-33 from the keratinocytes, which activate the mast cells to release IL-6. Furthermore, TLR-3 released from the keratinocytes interacts with IL-17 released from the mast cells to induce the release of IL-36γ and other inflammatory mediators. Mast cell-derived IL-17 activates downstream signaling cascade involving the activation of p38MAPK and NF-kB to induce the formation of new psoriatic lesions. Abbreviations: MAPK, mitogen-activated protein kinase; PAR, proteinase-activated receptor.