- A new study investigates gene expression
in the skin tissue of people with psoriasis.
- The researchers used a relatively new
technique called spatial transcriptomics.
- This approach helps map differences in
gene expression in healthy and affected skin.
- The researchers said they identified
immune cell changes between healthy and diseased skin.
Psoriasis
is one of the most common immune-mediated inflammatory diseases, affecting up
to 3% of people worldwide.
Aside
from its familiar dermatological symptoms, psoriasis also
affects other organs and systems.
People
with the condition have an increased risk of metabolic
syndrome, mental health conditions, and cardiovascular
problems.
In
addition, about 1 in 3 people with psoriasis develop psoriatic
arthritis.
How psoriasis spreads
throughout the body
While
scientists have made headway in understanding and treating psoriasis, it is not
yet clear why there are variations in symptoms between individuals.
Some
people with psoriasis have plaques on just a small part of the body while
others experience them over much larger sections of skin. Also, these plaques
can vary substantially in thickness, scaliness, and redness.
Evidence
shows that the risk of developing cardiovascular
disease and psoriatic arthritis increases with skin symptom severity.
Therefore,
it is vital to explore the mechanisms involved in symptom severity and how
localized skin inflammation leads to systemic disease.
A
recent study in the journal Science Immunology helps
fill in some missing pieces by employing spatial transcriptomics.
“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,” Dr. Jose
Scher, a study co-senior investigator and a specialist in psoriatic
disease at NYU Langone Health in New York, said in a press statement.
What is spatial
transcriptomics?
Spatial transcriptomics is a relatively new technology
that allows scientists to map cellular activity within human tissues precisely.
Standard
techniques to measure gene expression often involve homogenizing tissue
samples. This means that spatial information is lost.
With
spatial transcriptomics, however, scientists can analyze gene expression in
intact tissue. This provides detailed information about how gene expression
varies in different regions of the sample.
In
the current study, this technique allowed researchers to assess immune activity
in different regions and layers of skin.
Results from the study
on psoriasis spread
In
the recent study, the scientists collected tissue biopsies from the flank,
forearm, or buttocks of three healthy participants as well as 11 participants
with psoriasis.
In
total, the researchers analyzed 25 biopsies.
The
researchers reported that in more severe cases of psoriasis certain cells were
in different positions within the skin’s layers.
Immune
cells in samples from healthy participants were particularly prevalent around
follicles and blood vessels. However, these cells were closer to the skin’s
surface in samples from people with psoriasis.
In
particular, fibroblasts — a key source of inflammatory cytokines — and
macrophages were more common in the upper layers of skin in severe disease.
In
moderate-to-severe cases of psoriasis, the researchers noted increased gene
expression in molecular pathways associated with the control of lipid levels
and metabolism.
These
pathways play a role in various metabolic dysfunctions, including type 1
diabetes, nonalcoholic fatty liver disease, cholesterol metabolism, and
lipolysis in adipocytes.
The
researchers identified this uptick in expression in both psoriatic lesion
tissue and unaffected tissue from participants with psoriasis. This underlines
one of the challenges in studying psoriasis — even if drugs successfully treat
the more obvious external physical symptoms, molecular mechanisms may still be
working against overall health.
These
metabolic pathways, the authors suggest, may play some part in the increased risk
of diseases such as type 2 diabetes. However, researchers will need to carry
out more work to understand how this plays out.
The skin microbiome and
psoriasis
Follicles
are rich with commensal bacteria. They also act as a gateway for the entry of
allergens and pathogens. Follicular regions also richly express cytokines and
immune activation factors.
As
the authors explain, animal studies show that bacteria living in follicles are
important for immune surveillance. As an immune-mediated disease, these bacteria
could provide another piece of the psoriasis puzzle.
This
study demonstrated how immune cells are situated more distantly from follicles
in psoriatic samples, which could interrupt the healthy interaction between
commensals and the immune system.
Researchers
said understanding which microbes reside in follicular regions within healthy
and diseased skin might provide more insight.
Future study on the
spread of psoriasis
Researchers
said this study adds an important new tool for dermatology research because
spatial transcriptomics effectively defined biologically relevant, distinct
cellular “neighborhoods” in healthy skin.
“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,” said Shruti Naik,
PhD, a study senior co-investigator and an assistant professor in the
departments of pathology and medicine as well as the Ronald O. Perelman
Department of Dermatology at NYU Langone, in a press statement.
Medical
News Today spoke with Axel Svedbom,
PhD, a researcher at the Karolinska Institutet in Sweden who was not involved
in the study.
One
of the challenges of studying psoriasis, he explained, is that the condition
“is quite heterogenous and it is possible that grouping all patients with
psoriasis together masks important mechanisms that would be found if patients
were more carefully phenotyped.”
He
added that techniques, such as spatial transcriptomics, might help scientists
move toward this goal and build more specific treatment plans for individuals.
“I
think the next step is to move toward precision medicine. Combining data from
clinicians, patients, and the lab will help us to identify the right treatment
for the right patient and at the right time,” Svedbom said.
As technology advances and spatial transcriptomics gains higher resolution, the study authors said they hope to gather increasingly detailed information about skin in healthy and diseased states.
“Collectively, our findings underscore the value of spatially-resolved gene profiling in understanding emergent cellular ecosystems underlying health and disease,” they wrote.
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