061 Differential leukocyte migration towards chemotactic stimuli in psoriasis

Abstract

Psoriasis is a common disorder, characterised by excessive inflammation, leading to characteristic erythematous and scaly skin plaques. Leukocyte recruitment into, and retention within, the skin is a critical part of psoriasis pathogenesis. Though chemokines are the key regulators of leukocyte migration, and are upregulated in psoriasiform inflammation, little is known about their role in psoriasis. Additionally, though interactions of immune cells with keratinocytes have been previously linked to elevated production of multiple pro-inflammatory mediators, little is known about the sequence of leukocyte migratory events in psoriasis. We hypothesise that skin targeting neutrophils and T-cells collaborate with keratinocytes to orchestrate subsequent leukocyte recruitment in a chemokine-dependent manner. To test our hypothesis, we utilised a transwell system, to assay chemotactic responsiveness of leukocytes from psoriasis patients towards specific disease-relevant chemokines. Neutrophils derived from patients with psoriasis were more chemotactic towards psoriasis-associated chemokines than their healthy counterparts and neutrophil derived from patients with neutrophilic dermatoses. Furthermore, using supernatants from specific in-vitro co-cultures as chemoattractants in a novel sequential migration assay, our data suggest that psoriatic T-cell-keratinocyte interactions modulate subsequent neutrophil recruitment in vitro. We propose that chemokines are critical for the orchestration of leukocyte-keratinocyte interactions that propagate inflammation in psoriasis. More work is currently in progress to elucidate key mechanistic pathways, that can inform novel chemotaxis-targeting therapies in psoriasis and other inflammatory skin disorders.