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An "inflammatory memory' within the skin of patients with psoriasis could play a big role in reducing recurrence -- and even in finding a "cure" for the disease, according to a team of British researchers

A review in the offers insights into inflammatory memory and its underlying mechanisms and concludes that a better understanding of the phenomenon could one day mean more sustained psoriasis remission and reduced drug burden.

The following paper excerpts were edited for length and clarity.

What was the purpose of this review?

Biologic therapies including TNF, IL-17, and IL-23 inhibitors are available in routine care and are highly effective at achieving skin clearance in psoriasis. However, disease recurrence is sometimes observed at 12-34 weeks following drug withdrawal. The recurrence typically occurs at previously lesional sites, reinforcing the notion that "inflammatory memory" is retained within resolved psoriasis skin.

A persistent molecular shift in the skin (or 'molecular scar') following clinical resolution of psoriasis was first suggested in 2011. Recent research has advanced our understanding of inflammatory memory within tissues, indicating that it may be conferred by several interacting factors, including subcellular modifications (in DNA, RNA, and proteins) within multiple cell types and a remodeling of the affected tissue microenvironment.

For the current review, scientists explored data regarding inflammatory memory in resolved psoriasis skin and summarized research on the role of different cell types.

What were the review's primary findings or conclusions?

Epigenetic modifications appear to be a prevalent molecular mechanism underpinning inflammatory memory in multiple interacting cell types that reside in resolved psoriasis skin. Collectively, these cells have the potential to reactivate disease.

TRM cells are key contributors, as they are poised to trigger psoriasis inflammation and are long-lived in tissue. Whether psoriasis-specific TRM cells can be selectively targeted therapeutically remains unclear.

Epidermal Langerhans cells and dermal dendritic cells in resolved psoriasis skin can upregulate production of psoriasis-related cytokines. However, since these cells have a critical role in maintaining skin homeostasis and immunity, it may be difficult to target these subsets while mitigating adverse effects such as infection risk.

The diverse role of epithelial cells and fibroblasts is being increasingly recognized. Understanding the half-life and replicative potential of these cell types will help to uncover their long-term contribution to inflammatory memory.

What might a better understanding of inflammatory memory help dermatologists accomplish in the short or longer-term future?

The field of single-cell technologies is fast evolving and has the potential to deliver valuable insights on the complex heterogeneity of interacting cell types within resolved psoriasis skin and their relative contribution to disease recurrence.

In particular, single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) offer high-resolution, non-hypothesis-driven approaches to understanding changes in the transcriptome and epigenome across cell types within tissue. These can be complemented by spatial transcriptomic profiling and multiplexed protein imaging methods.

As these technologies evolve, an emerging challenge is to develop systems for integrating and analyzing large-scale datasets across three-dimensional space and time. If the promise of these methods is realized, we can expect unprecedented insights into the dynamic cellular and molecular changes contributing to inflammatory memory and the causal drivers of disease recurrence.

What could these kinds of evolutions ultimately mean for psoriasis patients?

This has the potential to reveal biomarkers of immune-mediated inflammatory disease recurrence and new therapeutic targets, enabling us to move closer to an ultimate goal of sustained drug-free remission (i.e., cure).