Unlocking the Mysteries of How Psoriasis May Spread

The Context: Psoriasis is an inflammatory skin condition whose biological origins remain unclear. Scientists know that severe forms of the disease can spread to other parts of the body and contribute to conditions like heart disease or diabetes, but how it does this, and how severe cases emerge to begin with, has not been well understood. 

The Study: By comparing the cellular activity of healthy versus inflamed skin, researchers at NYU Grossman School of Medicine led by NYSCF – Robertson Stem Cell Investigator Shruti Naik, PhD, found an increased amount of immune cells in the upper layers of the skin involved in cases of severe psoriasis. The team also found increased gene activity in pathways that influence metabolism and control of lipid levels, potentially explaining the development of other conditions such as heart disease and diabetes among psoriatic patients. 

The Importance: This study serves as the foundation for researchers and doctors to understand severe cases of psoriasis. It also offers an explanation as to why psoriatic patients are more prone to other life-threatening disorders such as arthritis and cardiovascular disease. 

Psoriasis, a chronic skin condition affecting millions worldwide, has long remained a puzzle for scientists and medical professionals. While psoriasis is primarily known for its visible symptoms, such as red patches and scales on the skin, there are many invisible aspects of the condition with more significant effects. 

Even in areas on the skin with no visible lesions, many individuals experience intense itching and discomfort. These persistent symptoms can negatively impact a person’s daily life and well-being, affecting their mood, sleep, and self-esteem. In some individuals with psoriasis, conditions may lead to arthritis, fatigue, heart diseases, and diabetes. 

The Cells Involved in Psoriasis

“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,” said the study’s co-corresponding author Jose U. Scher, MD in an article from NYU. 

The bulk of the mystery behind psoriasis comes from the spatial organization of the skin: the effects of psoriasis can be seen not only in areas with visible skin lesions but also in unaffected skin. Using a technique called spatial transcriptomics, which creates a kind of map showing where cells reside in a tissue, researchers were able to study and classify psoriatic skin samples, some of whom also had arthritis, as well as healthy skin samples. 

Researchers found that in people with severe psoriatic disease, cells called fibroblasts and macrophages were more abundant and located in the upper layers of the skin. Fibroblasts are cells that help regulate inflammation, and macrophages are a type of white blood cell, both vital in the healing process of our skin. This suggests that the distribution and presence of these cells may play an important role in the severity of psoriasis symptoms. 

In people with moderate-to-severe psoriasis, researchers found that certain genes associated with how our bodies process energy and control the levels of fats became more active. More importantly, these pathways are also related to diabetes and heart diseases, where these processes can malfunction. Surprisingly, this increased gene activity was observed even in healthy-looking skin that was far away from any visible psoriasis patches or sores, demonstrating the broad effects of inflammation in this disease. 

Paving the Way for Psoriasis Research

This study is only the beginning for uncovering and explaining the hidden factors of psoriasis: further research will be conducted to explain how symptoms go away on their own and why patients respond differently to the same anti-inflammatory medication. The team will also continue to explore how inflammation spreads to other parts of the body.

“Having found signals with potential systemic consequences, we are now working to understand how skin inflammation can lead to widespread disease affecting other organs,” said Dr. Scher.

The methods used in this study can also be used by other labs to explore skin conditions.

“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,” noted Dr. Naik.

Journal Article:

Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems
Rochelle L. Castill, Rochelle L Castillo, Ikjot Sidhu, Igor Dolgalev, Tinyi Chu, Aleksandr Prystupa, Ipsita Subudhi, Di Yan, Piotr Konieczny, Brandon Hsieh, Rebecca H Haberman, Shanmugapriya Selvaraj, Tomoe Shiomi, Rhina Medina, Parvathy Vasudevanpillai Girija, Adriana Heguy , Cynthia A Loomis, Luis Chiriboga, Christopher Ritchlin, Maria De La Luz Garcia-Hernandez, John Carucci, Shane A Meehan, Andrea L Neimann, Johann E Gudjonsson, Jose U Scher, Shruti Naik. Science Immunology. 2023. DOI:10.1126/sciimmunol.abq7991