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Concepts in psoriasis: psoriasis and the extracellular matrix

Authors


  • Funding sources
    None.

  • Conflicts of interest
    None declared.

John McFadden.
E-mail: john.mcfadden@kcl.ac.uk

Summary

Post-streptococcal guttate psoriasis only sometimes progresses to the persistent plaque psoriasis. We have previously proposed that psoriasis is driven by multiple extradomain A+ fibronectin (EDA+ FN) ‘feedback loops’. The psoriasis-specific loop, the ‘keratinocyte loop’, depends upon expression by keratinocytes of α5β1 integrin. In normal skin, α5β1 expression is minimal or absent in resting epithelial cells, where basal cells are anchored to the laminin component of the basement membrane (via integrins α6β4 and α3β1). However, when the laminin layer is disrupted, due to wounding for instance, α5β1 is then strongly expressed by basal cells as a means for anchoring. At uninvolved skin sites in patients with psoriasis the laminin layer within the basement membrane is disrupted, with a consequential increase in the expression by basal keratinocytes of EDA+ FN and α5β1. We are postulating that in guttate psoriasis streptococcal lytic enzymes, and in particular streptokinase, may – via plasminogen activation – initiate a disruption of the laminin layer in the basement membrane. It is also possible that the expression by proliferating keratinocytes of plasminogen-activating factor might result in additional laminin digestion. The suggestion is that progression of guttate psoriasis to full-blown plaque psoriasis, or to its spontaneous resolution, is governed largely by the triggering of humoral immune responses. Thus, if streptococcal lytic enzymes are neutralized by host antibodies in advance of irreversible and lasting damage to the basement membrane of the dermal papillae, then guttate psoriasis will resolve spontaneously. In contrast, if permanent damage is induced prior to effective neutralization of the relevant bacterial toxins, then keratinocytes will become chronically destabilized. The consequence will be to liberate keratinocytes to proliferate in response to various stimuli, and to continue to elaborate plasminogen activation enzymes; the combined effect being, in concert with immunological priming, to precipitate and sustain plaque psoriasis.

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