Evolutionary context of psoriatic immune skin response

Abstract

Abstract The skin is vital for protecting the body and perceiving external stimuli in the environment. Ability to adapt between environments is in part based on skin phenotypic plasticity, indicating evolved homeostasis between skin and environment. This homeostasis reflects the greater relationship between the body and the environment, and disruptions in this balance may lead to accumulation of susceptibility factors for autoimmune conditions like psoriasis. In this study, we examined the relationship between rapid, lineage-specific evolution of human skin and formation of psoriatic skin responses at the transcriptome level. We collected skin tissue biopsies from individuals with psoriasis and compared gene expression in psoriatic plaques to non-plaque psoriatic skin. We then compared these data with non-psoriatic skin transcriptome data from multiple primate species. We found 67 genes showing human-specific skin expression that are also differentially regulated in psoriatic skin; these genes are significantly enriched for skin barrier function, immunity and neuronal development. We identified six gene clusters with differential expression in the context of human evolution and psoriasis, suggesting underlying regulatory mechanisms in these loci. Human and psoriasis-specific enrichment of neuroimmune genes shows the importance of the ongoing evolved homeostatic relationship between skin and external environment. These results have implications for both evolutionary medicine and public health, using transcriptomic data to acknowledge the importance of an individual’s surroundings on their overall health.