The phrase "location, location, location" is commonly associated with real estate, but it also holds true in the study of human disease. Researchers are now focusing on understanding the specific locations of different cell types and how changes in their activity can impact overall health.
In a recent example, scientists funded by the National Institutes of Health (NIH) utilized advanced techniques to map immune cells within human skin to gain a more detailed understanding of psoriasis. Psoriasis is a chronic disease characterized by an overactive immune system, leading to inflammation of the skin. Individuals with psoriasis experience itchy, red, and flaky skin patches, which can vary in severity. Moreover, they are also at a higher risk of developing other health conditions such as psoriatic arthritis, diabetes, mental health issues, and heart problems, among others.
By mapping out cellular "neighborhoods" in human skin, researchers hope to better comprehend the progression of psoriasis and the differences between mild and severe forms of the disease. These maps may also provide insights into why people with psoriasis are more prone to developing other health problems compared to individuals without the condition.
In the study, conducted by a team from NYU Langone, New York, including Jose Scher and Shruti Naik, immune cells within 25 skin samples from 14 volunteers were analyzed. The participants included those with active psoriasis, individuals with psoriasis but no active skin lesions, and people with healthy skin without psoriasis. The researchers employed a sophisticated technique called spatial transcriptomics to examine cellular activity at the single-cell level within the samples.
In previous approaches to single-cell analysis, researchers would separate cells from the tissue they originated from. Although they could measure gene activity in individual cells, they couldn't piece together how these cells fit into the larger tissue context. Spatial transcriptomics now enables the molecular profiling of single cells to assess their activity in a tissue sample while simultaneously mapping their locations relative to other cells.
The study yielded interesting findings. For example, specific immune cells, particularly B cells, were found to migrate to the upper layers of the skin during active psoriasis. This is significant because previous studies struggled to adequately capture B cells in the skin, despite their suspected role in the disease.
Moreover, the spatial cellular maps revealed areas of inflammation in both actively inflamed skin and seemingly healthy skin. This finding emphasizes that psoriasis-related inflammation can affect not only the skin but also other parts of the body, even if not readily observable. In future studies, the researchers aim to explore how psoriasis and the immune cell activity changes underlying it may impact organs and tissues beyond the skin.
The detailed maps also indicated increased gene activity in numerous molecular pathways associated with metabolism and the regulation of lipid levels. This is particularly intriguing as these factors are known to be dysregulated in conditions like diabetes and heart disease, which occur more frequently in individuals with psoriasis. The altered activity was even observed in unaffected skin areas that were distant from any visible lesions.
With the identification of these signals that potentially have consequences for other parts of the body, the researchers are investigating how inflammatory immune cells and processes in the skin may contribute to more widespread disease processes affecting other organs. They plan to conduct similar studies with larger cohorts of individuals with and without active psoriasis lesions, as well as longitudinal studies to track individuals with psoriasis over time. Additionally, they will explore the reasons behind the varied responses to the same anti-inflammatory treatment regimens.
To expedite the process of discovery, the researchers have made their maps and associated data freely available as a resource for the scientific community. Psoriasis and associated psoriatic conditions affect approximately 7.5 million adults in the U.S. and millions more worldwide. The hope is that these maps will eventually contribute to guiding individuals with psoriasis towards a healthier future.
