cellular ecosystems
Mapping Immune Cell “Neighborhoods” in Psoriasis to Understand its Course
Posted on by Lawrence Tabak, D.D.S., Ph.D.
“Location, location, location.” While most of us know this phrase as a real estate adage, location—specifically that of various cell types—is becoming a key area of investigation in studying human disease. New techniques are enabling scientists to understand where certain cells are with respect to one another and how changes in their activity may affect your overall health.
In one recent example of the power of this approach, NIH-funded researchers [1] used a sophisticated method to map immune cells within human skin to get a more detailed picture of psoriasis, a common, chronic disease in which the immune system becomes overactive leading to skin inflammation. People with psoriasis develop patches of itchy, red, and flaky lesions on their skin, which can be mild to severe. For reasons that aren’t entirely clear, they’re also at higher risk for developing a wide range of other health conditions, including a unique form of arthritis known as psoriatic arthritis, diabetes, mental health issues, heart problems, and more.
The hope is that these newly drawn, precise maps of cellular “neighborhoods” in human skin will help chart the precise course of this disease to understand better the differences between mild and more severe forms. They may also yield important clues as to why people with psoriasis develop other health problems more often than people without psoriasis.
In the new study, a team including Jose Scher and Shruti Naik, NYU Langone, New York, analyzed immune cells within 25 skin samples from 14 volunteers, including those with active psoriasis, those with psoriasis but no active lesions, and people with healthy skin who do not have psoriasis. The researchers relied on a sophisticated approach called spatial transcriptomics [2] to map out what happens at the single-cell level within the samples.
In earlier approaches to single-cell analysis, researchers first would separate cells from the tissue they came from. While they could measure gene activity within those cells at the individual level, they couldn’t put things back together to see how they all fit. With spatial transcriptomics, it’s now possible to molecularly profile single cells to measure their activity in a tissue sample while also mapping their locations with respect to other cells.
The new study led to some intriguing findings. For instance, certain immune cells, specifically B cells, moved to the upper layers of the skin during active disease. That’s notable because prior studies had been unable to capture B cells in the skin adequately, and these cells are thought to play an important role in the disease.
Interestingly, the spatial cellular maps revealed inflammatory regions in both actively inflamed skin and in skin that appeared healthy. This finding highlights the fact that the inflammation that goes with psoriasis can affect the skin, and likely other parts of the body, in ways that aren’t easily observed. In future studies, the researchers want to explore how the presence of psoriasis and its underlying changes in immune cell activity may influence other organs and tissues beneath the skin.
Their fine-scale maps also showed increased gene activity in dozens of molecular pathways that are tied to metabolism and the control of lipid levels. That’s especially interesting because these factors are known to go awry in diabetes and heart conditions, which happen more often in people with psoriasis compared to those without. They also could see in their maps that this altered activity sometimes occurred in clear skin distant from any apparent lesions.
Having discovered such signals with potential consequences for other parts of the body, the researchers report that they’re working to understand how inflammatory immune cells and processes in the skin may lead to more widespread disease processes that affect other parts of the body. They plan to conduct similar studies in larger groups of people with and without active psoriasis lesions and studies following individuals with psoriasis over time. They’ll also explore questions about why people respond differently to the same anti-inflammatory treatment regimens.
To speed the process of discovery, they’ve made their maps and associated data freely available as a resource for the scientific community. About 7.5 million adults in the U.S. and millions more worldwide have psoriasis and associated psoriatic conditions [3]. The hope is that these maps will one day help to steer them toward a healthier future.
References:
[1] 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.
[2] Method of the Year: spatially resolved transcriptomics. Marx V. Nat Methods. 2021 Jan;18(1):9-14. doi: 10.1038/s41592-020-01033-y.
[3] Psoriasis Prevalence in Adults in the United States. Armstrong AW, Mehta MD, Schupp CW, Gondo GC, Bell SJ, Griffiths CEM. JAMA Dermatol. 2021 Aug 1;157(8):940-946. doi: 10.1001/jamadermatol.2021.2007.
Links:
Psoriasis (National Institute of Arthritis and Musculoskeletal and Skin Diseases/NIH)
Jose Scher (NYU Langone Health, New York, NY)
Shruti Naik (NYU Langone Health, New York, NY)
NIH Support: National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences, National Institute of Allergy and Infectious Diseases
