When the immune system targets the skin

Psoriasis is one of the most common chronic inflammatory skin diseases, affecting an estimated 2–4% of the global population [4]. The disease is driven by dysregulated immune responses, including T-lymphocyte hyperactivation and excessive production of proinflammatory cytokines—most notably interleukins IL-17 and IL-23, as well as tumor necrosis factor-alpha (TNF-α). These processes stimulate abnormal keratinocyte proliferation and contribute to the formation of characteristic plaques [2].

Psoriasis is no longer viewed solely as a skin disease. Patients with psoriasis are more likely to have components of metabolic syndrome, including dyslipidemia, insulin resistance, and hypertension [3]. At the same time, the precise biochemical changes occurring directly within lesional skin have remained only partially characterized. Metabolomics—the simultaneous measurement of hundreds or thousands of low-molecular-weight compounds in a biological sample—makes it possible to build an integrated picture of tissue-level chemical changes and identify molecular signatures of disease.

Study design and methodology

In a large-scale study published in the International Journal of Biological Sciences in 2026, an international research team performed comprehensive metabolomic profiling of skin samples from patients with psoriasis [1]. The authors integrated the chemical data with gene expression analysis (transcriptomics) and experimentally evaluated their key findings.

The study included 60 skin samples: 30 from psoriatic lesions and 30 from healthy volunteers. To characterize the chemical composition of the tissue, the researchers used high-resolution analytical techniques, including liquid chromatography and high-resolution mass spectrometry. In simple terms, these methods act like a highly sophisticated scanner: they separate the complex mixture of substances in a skin sample into individual components and measure each molecule with a high degree of precision. Wide-targeted metabolomics enabled the researchers to detect and quantify hundreds of known biological compounds simultaneously, producing a detailed chemical profile of psoriatic skin.

To determine which changes were associated with the disease, the authors compared metabolite levels in lesional and healthy skin and identified the most significant differences. They then matched these findings with data on gene activity across different skin cell types. This approach helped link the observed chemical shifts to specific cells, particularly differentiated keratinocytes.

For the final experimental validation, the researchers used a mouse model of psoriasis-like dermatitis. In seven-week-old C57BL/6 mice, a patch of dorsal skin was shaved, and 5% imiquimod cream was applied once daily for 4–5 days to induce inflammation resembling the psoriatic process. At the same time, the animals received intraperitoneal injections of citrate, L-tyrosine, or purine; control groups received the corresponding vehicle without the test compound. Citrate and L-tyrosine were administered daily, whereas purine was given every other day. The animals’ body weight and skin changes were monitored, and after the experiment the researchers assessed epidermal thickness, inflammatory gene activity, and the composition of immune cells in the skin.

A comprehensive metabolic map of psoriatic skin

The analysis identified 707 metabolites in psoriatic skin whose levels differed significantly from those in healthy tissue. These compounds belonged to 21 classes. The largest groups among the altered molecules were amino acids and their derivatives (31.68%), fatty acids (13.01%), organic acids (11.31%), and nucleotides (9.34%).

The most pronounced abnormalities involved nucleotide and pyrimidine metabolism. The transcriptomic analysis supported these findings: lesional skin showed increased expression of genes encoding several key enzymes in these pathways, including thymidine kinase 1 (TK1), cytidine triphosphate synthetase 1 (CTPS1), and ribonucleotide reductase M2 (RRM2).

Taken together, the data indicated that inflammatory keratinocytes were the main source of these chemical shifts. Previous research had already identified altered lipid metabolism in keratinocytes as an important component of psoriasis pathogenesis [5]. The present study expands this picture by pointing to nucleotide and pyrimidine metabolism as additional, potentially important components of the disease process.

Three markers of disease severity

To search for biomarkers of disease activity, the authors compared metabolite levels with clinical measures: the Psoriasis Area and Severity Index (PASI) and body surface area involvement (BSA). They found that the levels of three compounds—citrate, L-tyrosine, and purine—were closely and positively associated with psoriasis severity: the higher the PASI score, the greater the levels of these compounds in the skin.

The findings were then tested in mice using a model of imiquimod-induced psoriasis-like dermatitis. In this model, systemic administration of citrate and L-tyrosine intensified skin inflammation and was accompanied by weight loss compared with the control group. Under these experimental conditions, purine did not show a pronounced pathogenic effect. The results were assessed using multiplex immunofluorescence, quantitative PCR, and flow cytometry.

Can these findings be applied to cosmetic products?

The results cannot be directly extrapolated to topical cosmetic products. In the mouse experiment, citrate and L-tyrosine were administered systemically by intraperitoneal injection rather than applied to the skin. In addition, the study did not evaluate cosmetic formulations, concentrations, or topical delivery methods for these compounds. Therefore, the findings do not provide a basis for concluding that cosmetic products containing related ingredients can cause or aggravate psoriasis in humans.

Limitations

The authors identified several limitations:

1. The sample size was relatively small, which may have affected the statistical power of the analysis.
2. The biopsy samples from lesional skin did not allow the patient and healthy volunteer groups to be perfectly matched for sex, age, and body mass index.
3. The metabolomic approach provided relative rather than absolute quantification of the metabolites.
4. A substantial proportion of the identified compounds remained insufficiently characterized, and targeted mass-spectrometric detection was not performed for some metabolites.

Clinical and therapeutic significance

The study is potentially important in two main respects.

From a clinical perspective, the identification of citrate and L-tyrosine as molecules whose levels correlate with psoriasis severity according to PASI and BSA raises the possibility of developing objective biochemical measures of disease activity and monitoring treatment response. Such measures could eventually complement the clinical scoring systems already used in practice.

From a therapeutic perspective, the apparent involvement of nucleotide and pyrimidine metabolism, together with the identification of specific enzymes in these pathways—including TK1, CTPS1, RRM2, and others—points to potential molecular targets for pharmacologic intervention. The finding that differentiated keratinocytes, particularly their inflammatory subtype, are the primary source of the metabolic abnormalities may help define the cellular focus of future therapeutic strategies.

Conclusion

This study describes a comprehensive metabolic map of psoriatic skin, identifying 707 compounds with altered levels and pointing to nucleotide and pyrimidine metabolism as key disrupted pathways.

Citrate, L-tyrosine, and purine were positively correlated with clinical measures of disease severity, whereas only citrate and L-tyrosine intensified inflammation in the mouse model used in the study.

By integrating metabolomics, transcriptomics, and single-cell sequencing, the researchers provide new insight into the role of keratinocytes and cellular metabolism in psoriasis pathogenesis.

These findings may serve as a basis for further research into biomarkers of disease activity and potential therapeutic targets. However, larger studies with absolute quantification of metabolites will be needed to validate the results clinically.

Refernces

1. Zhu P., Wang Y., Sun J. et al. Comprehensive metabolomic profiling of skin lesions from psoriasis patients reveals disease signatures. Int J Biol Sci 2026; 22(11): 5934–5952.
2. Guo J., Zhang H., Lin W. et al. Signaling pathways and targeted therapies for psoriasis. Signal Transduct Target Ther 2023; 8(1): 437.
3. Snekvik I., Nilsen T.I.L., Romundstad P.R., Saunes M. Metabolic syndrome and risk of incident psoriasis: prospective data from the HUNT Study, Norway. Br J Dermatol 2019; 180(1): 94–99.
4. Garner K.K., Hoy K.D.S., Carpenter A.M. Psoriasis: recognition and management strategies. Am Fam Physician 2023; 108(6): 562–573.
5. Cai J., Zhou X., Zhuang Y. et al. Reprogramming of fatty acid metabolism via PPARalpha-orchestrated FADS2 in keratinocytes modulates skin inflammation in psoriasis. Adv Sci (Weinh) 2025; 12(40): e17049.