June 13, 2023

A cellular and molecular understanding of psoriasis

At a Glance

  • Researchers gained new insights into the cellular and molecular features of psoriasis, an inflammatory skin disease.
  • The findings may help to understand how severe skin inflammation at one site can lead to problems in other sites of the body.
Flaky, red skin on person’s elbows. In psoriasis, overactive immune cells release molecules that set off the rapid production of skin cells, leading to inflamed and scaly skin. SNAB / Shutterstock

Psoriasis is an inflammatory skin disease that affects 2-3% of the population. The disease is characterized by thickened, red, scaly lesions on the skin. It may also lead to systemic complications, such as cardiovascular disease, depression, and joint inflammation (which is called psoriatic arthritis and affects up to 30% of those with psoriasis). Many cellular and molecular changes have been identified in the skin of people with psoriasis. But it’s not known how the various immune cells involved are distributed within the skin and how these differ between healthy and diseased skin, or whether they differ in psoriatic arthritis.

To find out, an NIH-funded research team led by Drs. Jose U. Scher and Shruti Naik at NYU Langone Health used a technique called spatial transcriptomics. This technique identifies different cell types based on which genes in the cells are turned on or off. It also shows the relative locations of those cell types in tissues. The team analyzed 25 skin samples from people with and without psoriasis. From those with psoriasis, they included samples from skin with and without lesions and from those with and without psoriatic arthritis. The results appeared in Science Immunology on June 2, 2023.

The researchers found that healthy and lesioned skin differed significantly. Lesions contained inflamed areas in both the outer and inner skin layers. In healthy skin, some immune cells (mainly dendritic cells and T lymphocytes) were concentrated in and around hair follicles, and B cells (which produce antibodies) were absent entirely. By contrast, lesions had various immune cells, including B cells, throughout the upper skin layers.

The researchers were also able to identify tissue differences between apparently healthy skin in people with and without psoriasis. This suggests that the effects of psoriatic inflammation extend beyond individual lesions.

The team couldn’t distinguish between people with and without psoriatic arthritis using their data. But they could distinguish mild psoriasis cases from those that were moderate to severe. In people with mild psoriasis, certain cells called fibroblasts were enriched in the upper skin layers. In moderate-to-severe psoriasis, fibroblasts remained deeper in the skin.

Gene activity also varied with disease severity. In moderate to severe psoriasis, activity in genes involved in lipid metabolism pathways was elevated. These pathways included ones known to go awry in metabolic disorders like diabetes and fatty liver disease. The researchers observed these changes in skin outside of lesions as well as within lesions.

The findings demonstrate the value of spatial transcriptomics for understanding inflammatory skin diseases. “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 says.

The researchers hope that the results will inform further studies into how inflammation in one site of the skin can lead to complications elsewhere in the body.

—by Brian Doctrow, Ph.D.

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References: Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems. Castillo RL, Sidhu I, Dolgalev I, Chu T, Prystupa A, Subudhi I, Yan D, Konieczny P, Hsieh B, Haberman RH, Selvaraj S, Shiomi T, Medina R, Girija PV, Heguy A, Loomis CA, Chiriboga L, Ritchlin C, Garcia-Hernandez ML, Carucci J, Meehan SA, Neimann AL, Gudjonsson JE, Scher JU, Naik S. Sci Immunol. 2023 Jun 8;8(84):eabq7991. doi: 10.1126/sciimmunol.abq7991. Epub 2023 Jun 2. PMID: 37267384.

Funding: NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Allergy and Infectious Disease (NIAID), and National Cancer Institute (NCI); National Psoriasis Foundation; Group for Research and Assessment of Psoriasis and Psoriatic Arthritis; Rheumatology Research Foundation; Pew Charitable Trusts; NYU Langone Health; New York Stem Cell Foundation; David and Lucille Packard Foundation; Beatrice Snyder Foundation; Riley Family Foundation; NYU Colton Center for Autoimmunity.