Psoriasis exhibits hidden features of inflammation such as altered cellular clusters and increased gene activity in metabolic pathways, according to recent findings, which may explain the systemic effects and comorbidities associated with the condition.¹

These findings may end up allowing scientists to better understand why this skin disease can work as a trigger to other seemingly-unrelated issues, such as heart disease, inflammatory bowel disease, and type 2 diabetes.

This research was led by Shruti Naik, PhD, an assistant professor in the departments of Pathology, Medicine, and in the Ronald O. Perelman Department of Dermatology at New York University Langone.

Naik and a team of other researchers at NYU Grossman School of Medicine explored some of the hidden aspects of inflammation associated with psoriatic disease, specifically the systemic effects of psoriasis and its potential links to other conditions.

"Our initial goal was to find measurable molecular signals that could tell us who is more likely to develop severe psoriasis, as well as who is at higher risk of developing related disorders that often accompany psoriasis, such as arthritis and cardiovascular disease," co-senior investigator Jose Scher, MD, said in a statement.²

Background and Findings

The investigators focused on small areas of skin inflammation and the ways in which this condition can lead to wide-ranging effects throughout the body. The study focused on investigating psoriasis as an immune-mediated condition that commonly affects areas beyond the skin.

The research team used intact skin samples taken from 11 men and women with reported cases of mild to severe psoriatic disease, in addition to 3 healthy adults without diagnosis of psoriasis.

The team conducted spatial transcriptomics (ST) analyses—a technique that examines molecular and cellular interactions within a specific tissue—on the biopsies from healthy participants, the ones with active psoriatic lesions, and ones with clinically uninvolved skin,

The researchers were consequently able to discover significant variations in immune microniches between healthy and inflamed skin. The team, to enhance their study’s findings, integrated their newfound data with single-cell transcriptomics data that was publicly available.

The team identified notable differences in the location of fibroblasts and macrophages, both essential regulators of inflammation. In more severe cases of psoriasis, these clusters of cells were found to be more common in the upper layers of the skin.

Furthermore, the findings showed higher gene activity in over 3 dozen molecular pathways which related to both metabolism and to lipid control in skin samples from those with moderate-to-severe psoriasis.

These factors, the research team noted, are known to be implicated in conditions like diabetes and cardiovascular diseases. The heightened gene activity was even noted in unaffected skin areas far from any visible lesions.

Scher, a co-senior investigator of the study, emphasized the initial goal of identifying measurable molecular signals that can predict the development of severe psoriasis and associated disorders. The team is set to now focus on exploring how skin inflammation may trigger systemic diseases which affect other organs.

"Our study serves as a valuable resource for the scientific community, offering the most comprehensive archive of cellular and molecular features involved in both diseased and healthy skin,” Naik explained in a statement.

The investigators note that future studies will involve larger groups of patients and assess lesioned and nonlesioned skin from the same individuals to explore why some respond differently to the same anti-inflammatory medications and why the disease can spontaneously clear in some cases.

References

1. ^{Rochelle L. Castillo et al. ,Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems.Sci. Immunol. 8, eabq7991 (2023). DOI:10.1126/sciimmunol.abq7991.}
2. ^{PR Newswire. Study helps explain what drives psoriasis severity and offers clues as to how disease may spread to other body parts. PR Newswire. [Internet]. 2023 Jun 3. Available from: https://prnmedia.prnewswire.com/news-releases/study-helps-explain-what-drives-psoriasis-severity-and-offers-clues-as-to-how-disease-may-spread-to-other-body-parts-301835348.html.}