Psoriasis Pathogenesis and Treatment Approaches

Psoriasis is a chronic immune‐mediated skin disorder characterised by hyperproliferation of keratinocytes and dysregulated interactions between innate and adaptive immune cells. Genetic susceptibility and environmental triggers converge on key signalling circuits—most notably the interleukin-23/interleukin-17 (IL-23/Th17) axis—leading to sustained inflammation, epidermal remodelling and systemic comorbidities such as cardiovascular disease and metabolic syndrome. The pathological interplay involves dendritic cells, T helper cell subsets, neutrophils and keratinocytes, with cytokines like tumour necrosis factor-α, interferon-γ and IL-17 driving the chronic inflammatory loop. Treatment strategies have evolved from broad immunosuppression to highly targeted interventions: topical agents and phototherapy remain first-line for mild disease; systemic small-molecule inhibitors, including phosphodiesterase-4 inhibitors, address moderate-to-severe presentations; and biologic therapies that selectively neutralise TNF-α, IL-12/23 or IL-17 have revolutionised long-term control. Emerging approaches exploit advances in genetics, microbiome modulation and cell-based therapies, aiming to deepen remission, reduce relapse and tailor management to individual risk profiles.

Research from Nature Portfolio

Whole-exome sequencing of paired lesional and non-lesional epidermis has revealed that keratinocyte mutation rates remain modest in psoriasis and that there is no large-scale clonal expansion of driver mutations, but a distinct signature of psoralen-induced DNA damage is evident in patients treated with PUVA photochemotherapy, informing future safety considerations. A large-scale meta-analysis of genome-wide association studies has expanded the number of susceptibility loci to over sixty, implicating interferon signalling and NFκB pathways, and demonstrating enrichment of risk variants in regulatory regions of CD4+ and CD8+ T-cell subsets. The derived genetic risk score correlates with age at onset and offers a framework for personalised risk stratification and early intervention.

Psoriasis Pathogenesis and Treatment Approaches publication trend

The graph below shows the total number of articles in psoriasis pathogenesis and treatment approaches across all publications each year (not limited to Nature Index journals).

Technical terms

IL-17: A proinflammatory cytokine produced principally by Th17 cells that stimulates keratinocyte proliferation and chemokine release.

IL-23: A cytokine that promotes differentiation and maintenance of Th17 cells, sustaining chronic inflammation.

Th17 cell: A subset of CD4+ T helper lymphocytes characterised by secretion of IL-17 and linked to autoimmune pathology.

Keratinocyte: The predominant epithelial cell in the epidermis responsible for barrier formation and target of inflammatory mediators.

Genome-wide association study: A research approach that scans entire genomes for common genetic variants associated with a particular disease.

Somatic mutation: A genetic alteration acquired by a non-germline cell that can contribute to disease processes when present in tissue compartments.

References

1. Signaling pathways and targeted therapies for psoriasis. Signal Transduction and Targeted Therapy (2023).
2. Effects of psoriasis and psoralen exposure on the somatic mutation landscape of the skin. Nature Genetics (2023).
3. Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. Nature Communications (2017).
4. The Interplay Between Keratinocytes and Immune Cells in the Pathogenesis of Psoriasis. Frontiers in Immunology (2018).
5. Risk Factors for the Development of Psoriasis. International Journal of Molecular Sciences (2019).
6. Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. Cellular Signalling (2014).