CoChat
Sign Up
Cited by 12

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Spatial Proteomic Profiling Reveals Increased Levels of Cholesterol Synthesis Proteins in Psoriasis Vulgaris

Møller, Line B.P., Kromann, Bjørn, Kabatnik, Sonja, Hjortlund, Johanne Hatorp, Haulrig, Morten Bahrt, Sølberg, Julie B.K., Bzorek, Michael, Clark, Rachael A., Skov, Lone, Mann, Matthias, Løvendorf, Marianne Bengtson, Dyring-Andersen, Beatrice·2025·Journal of Investigative Dermatology
DOI 10.1016/j.jid.2025.05.002
Open this paper in CoChat — free account

Abstract

Psoriasis arises from a combination of genetic and environmental factors, triggering inflammatory circuits involving innate and adaptive immune responses. Although the associated histological changes are well-described, the changes on the protein level associated with the inflammation and tissue remodeling have only been characterized to a limited extent and with a low degree of spatial information. Therefore, we aimed to explore skin layer-specific proteomic changes in psoriatic plaques. Using laser-capture microdissection, we divided skin biopsies from patients with psoriasis (n = 8) and healthy controls (n = 8) into 4 layers (stratum corneum, inner epidermis, dermis, and subcutis) and analyzed the protein composition of each layer using mass spectrometry. A total of 7236 proteins were identified, and 1649 proteins were differentially expressed in lesional versus nonlesional inner epidermis. Several of the upregulated proteins related to innate immunity and cholesterol biosynthesis. Stratum corneum showed a more complex protein composition in psoriatic lesions compared with that in controls, whereas dermis exhibited upregulation of proteins involved in IL-17 signaling and neutrophil chemotaxis. No differences were detected in subcutis. Our findings highlight the inner epidermis as central to psoriasis pathology, driven by both innate and adaptive immune mechanisms that are potentially enhanced by an increased cholesterol production.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.jid.2025.05.002

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Cholesterol homeostasis is disrupted in psoriatic lesions, with upregulation of cholesterol synthesis pathways, elevated free cholesterol, and disrupted cellular cholesterol homeostasis.

    “spatial proteomic and biochemical analyses demonstrate significant upregulation of cholesterol synthesis pathways, elevated free cholesterol levels, and disrupted cellular cholesterol homeostasis14–17.”

    From Macrophage INSIG1 deficiency drives psoriasiform dermatitis via the SREBP2-STAT1 axis (2026) · cites this paper as [14]

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 56

  1. Aleid, 2024, The impact of statins on disease severity and quality of life in patients with psoriasis: a systematic review and meta-analysis, Healthcare (Basel), 12, 1526, 10.3390/healthcare12151526 · DOI
  2. Bewley, 2014, Identifying individual psychosocial and adherence support needs in patients with psoriasis: a multinational two-stage qualitative and quantitative study, J Eur Acad Dermatol Venereol, 28, 763, 10.1111/jdv.12174 · DOI
  3. Boonpethkaew, 2022, Transcriptomic profiling of peripheral edge of lesions to elucidate the pathogenesis of psoriasis vulgaris, Int J Mol Sci, 23, 4983, 10.3390/ijms23094983 · DOI
  4. Brunner, 2022, Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation, Mol Syst Biol, 18, 10.15252/msb.202110798 · DOI · Paper page
  5. Cai, 2019, A critical role of the IL-1β-IL-1R signaling pathway in skin inflammation and psoriasis pathogenesis, J Invest Dermatol, 139, 146, 10.1016/j.jid.2018.07.025 · DOI
  6. Castillo, 2023, Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems, Sci Immunol, 8, 10.1126/sciimmunol.abq7991 · DOI
  7. Chignell, 2006, Ultraviolet A sensitivity in Smith-Lemli-Opitz syndrome: possible involvement of cholesta-5,7,9(11)-trien-3 beta-ol, Free Radic Biol Med, 41, 339, 10.1016/j.freeradbiomed.2006.04.021 · DOI · Paper page
  8. Christmann, 2020, Interleukin 17 promotes expression of alarmins S100A8 and S100A9 during the inflammatory response of keratinocytes, Front Immunol, 11
  9. Demichev, 2020, DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput, Nat Methods, 17, 41, 10.1038/s41592-019-0638-x · DOI
  10. Demichev, 2022, dia-PASEF data analysis using FragPipe and DIA-NN for deep proteomics of low sample amounts, Nat Commun, 13, 3944, 10.1038/s41467-022-31492-0 · DOI
  11. Deutsch, 2023, The ProteomeXchange Consortium at 10 years: 2023 update, Nucleic Acids Res, 51, D1539, 10.1093/nar/gkac1040 · DOI
  12. Dyring-Andersen, 2020, Spatially and cell-type resolved quantitative proteomic atlas of healthy human skin, Nat Commun, 11, 5587, 10.1038/s41467-020-19383-8 · DOI
  13. Fessler, 2015, Regulation of adaptive immunity in health and disease by cholesterol metabolism, Curr Allergy Asthma Rep, 15, 48, 10.1007/s11882-015-0548-7 · DOI
  14. Fredman, 2022, Towards precision dermatology: emerging role of proteomic analysis of the skin, Dermatology, 238, 185, 10.1159/000516764 · DOI
  15. Gao, 2020, Discovering novel hub genes and pathways associated with the pathogenesis of psoriasis, Dermatol Ther, 33, 10.1111/dth.13993 · DOI
  16. Gniadecki, 2023, Architecture of skin inflammation in psoriasis revealed by spatial transcriptomics, Clin Immunol, 256, 10.1016/j.clim.2023.109771 · DOI
  17. Guttman-Yassky, 2007, Psoriasis: evolution of pathogenic concepts and new therapies through phases of translational research, Br J Dermatol, 157, 1103, 10.1111/j.1365-2133.2007.08135.x · DOI
  18. Iversen, 2017, PSO p27, a SERPINB3/B4-derived protein, is most likely a common autoantigen in chronic inflammatory diseases, Clin Immunol, 174, 10, 10.1016/j.clim.2016.11.006 · DOI
  19. Izuhara, 2018, Squamous cell carcinoma antigen 2 (SCCA2, SERPINB4): an emerging biomarker for skin inflammatory diseases, Int J Mol Sci, 19, 1102, 10.3390/ijms19041102 · DOI
  20. Jabbari, 2012, Transcriptional profiling of psoriasis using RNA-seq reveals previously unidentified differentially expressed genes, J Invest Dermatol, 132, 246, 10.1038/jid.2011.267 · DOI
  21. Kabatnik, 2024, Spatial characterization and stratification of colorectal adenomas by deep visual proteomics, iScience, 27, 10.1016/j.isci.2024.110620 · DOI
  22. Karlsson, 2021, A single-cell type transcriptomics map of human tissues, Sci Adv, 7, 10.1126/sciadv.abh2169 · DOI · Paper page
  23. Kong, 2017, MSFragger: ultrafast and comprehensive peptide identification in mass spectrometry-based proteomics, Nat Methods, 14, 513, 10.1038/nmeth.4256 · DOI
  24. Kromann, 2024, Proteins in the skin and blood in patients with psoriasis: a systematic review of proteomic studies, Dermatology, 240, 317, 10.1159/000533981 · DOI
  25. Luo, 2023, Crosstalk between cholesterol metabolism and psoriatic inflammation, Front Immunol, 14
  26. Ma, 2020, Antimicrobial peptides: bridging innate and adaptive immunity in the pathogenesis of psoriasis, Chin Med J (Engl), 133, 2966, 10.1097/CM9.0000000000001240 · DOI
  27. Martin, 2023, Novel therapies in plaque psoriasis: a review of tyrosine kinase 2 inhibitors, Dermatol Ther (Heidelb), 13, 417, 10.1007/s13555-022-00878-9 · DOI
  28. Méhul, 2017, Noninvasive proteome analysis of psoriatic stratum corneum reflects pathophysiological pathways and is useful for drug profiling, Br J Dermatol, 177, 470, 10.1111/bjd.15346 · DOI
  29. Meier, 2020, diaPASEF: parallel accumulation-serial fragmentation combined with data-independent acquisition, Nat Methods, 17, 1229, 10.1038/s41592-020-00998-0 · DOI
  30. Misiorek, 2016, Keratin 8-deletion induced colitis predisposes to murine colorectal cancer enforced by the inflammasome and IL-22 pathway, Carcinogenesis, 37, 777, 10.1093/carcin/bgw063 · DOI
  31. Noda, 2015, The translational revolution and use of biologics in patients with inflammatory skin diseases, J Allergy Clin Immunol, 135, 324, 10.1016/j.jaci.2014.11.015 · DOI
  32. Nussbaum, 2021, Role of regulatory T cells in psoriasis pathogenesis and treatment, Br J Dermatol, 184, 14, 10.1111/bjd.19380 · DOI
  33. Patel, 2007, A review of high-dose statin therapy: targeting cholesterol and inflammation in atherosclerosis, Eur Heart J, 28, 664, 10.1093/eurheartj/ehl445 · DOI
  34. Perez-Riverol, 2025, The PRIDE database at 20 years: 2025 update, Nucleic Acids Res, 53, D543, 10.1093/nar/gkae1011 · DOI
  35. Politiek, 2021, Compromised protein prenylation as pathogenic mechanism in mevalonate kinase deficiency, Front Immunol, 12, 10.3389/fimmu.2021.724991 · DOI
  36. Rao, 2021, Exploring tissue architecture using spatial transcriptomics, Nature, 596, 211, 10.1038/s41586-021-03634-9 · DOI · Paper page
  37. Raposo, 2015, Antiviral gene expression in psoriasis, J Eur Acad Dermatol Venereol, 29, 1951, 10.1111/jdv.13091 · DOI
  38. Ryckman, 2003, Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion, J Immunol, 170, 3233, 10.4049/jimmunol.170.6.3233 · DOI
  39. Sivaprasad, 2015, SERPINB3/B4 contributes to early inflammation and barrier dysfunction in an experimental murine model of atopic dermatitis, J Invest Dermatol, 135, 160, 10.1038/jid.2014.353 · DOI
  40. Sloma, 2008, Regulation of CD1a surface expression and antigen presentation by invariant chain and lipid Rafts, J Immunol, 180, 980, 10.4049/jimmunol.180.2.980 · DOI
  41. Socha, 2020, The effect of statins on psoriasis severity: a meta-analysis of randomized clinical trials, Arch Med Sci, 16, 1, 10.5114/aoms.2019.90343 · DOI
  42. Swindell, 2018, RNA-seq analysis of IL-1B and IL-36 responses in epidermal keratinocytes identifies a shared MyD88-dependent gene signature, Front Immunol, 9, 80, 10.3389/fimmu.2018.00080 · DOI
  43. Swindell, 2015, Proteogenomic analysis of psoriasis reveals discordant and concordant changes in mRNA and protein abundance, Genome Med, 7, 86, 10.1186/s13073-015-0208-5 · DOI
  44. Swindell, 2017, RNA-seq identifies a diminished differentiation gene signature in primary monolayer keratinocytes grown from lesional and uninvolved psoriatic skin, Sci Rep, 7, 10.1038/s41598-017-18404-9 · DOI
  45. Takeda, 2002, Overexpression of serpin squamous cell carcinoma antigens in psoriatic skin, J Invest Dermatol, 118, 147, 10.1046/j.0022-202x.2001.01610.x · DOI
  46. Takeshita, 2017, Psoriasis and comorbid diseases: epidemiology, J Am Acad Dermatol, 76, 377, 10.1016/j.jaad.2016.07.064 · DOI
  47. Tervaniemi, 2016, NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis, Sci Rep, 6, 10.1038/srep22745 · DOI
  48. Tyanova, 2016, The Perseus computational platform for comprehensive analysis of (prote)omics data, Nat Methods, 13, 731, 10.1038/nmeth.3901 · DOI · Paper page
  49. Varshney, 2016, Transcriptome profiling unveils the role of cholesterol in IL-17A signaling in psoriasis, Sci Rep, 6, 10.1038/srep19295 · DOI · Paper page
  50. Varshney, 2018, PI3K/AKT/mTOR activation and autophagy inhibition plays a key role in increased cholesterol during IL-17A mediated inflammatory response in psoriasis, Biochim Biophys Acta Mol Basis Dis, 1864, 1795, 10.1016/j.bbadis.2018.02.003 · DOI
  51. Wang, 2017, Proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction, Mol Cell Proteomics, 16, 121, 10.1074/mcp.M116.060301 · DOI
  52. Wolk, 2013, IL-29 is produced by T(H)17 cells and mediates the cutaneous antiviral competence in psoriasis, Sci Transl Med, 5, 10.1126/scitranslmed.3006245 · DOI
  53. Yan, 2023, Exhaustion-associated cholesterol deficiency dampens the cytotoxic arm of antitumor immunity, Cancer Cell, 41, 1276, 10.1016/j.ccell.2023.04.016 · DOI
  54. Zhang, 2024, AP-2α/AP-2β transcription factors are key regulators of epidermal homeostasis, J Invest Dermatol, 144, 1505, 10.1016/j.jid.2023.12.017 · DOI
  55. Zhang, 2019, Keratin 6, 16 and 17-critical barrier alarmin molecules in skin wounds and psoriasis, Cells, 8, 807, 10.3390/cells8080807 · DOI
  56. Raposo, 2015, Antiviral gene expression in psoriasis, J Eur Acad Dermatol Venereol, 29, 1951, 10.1111/jdv.13091 · DOI

Cited by

Sorted by citations

Metadata

Authors
Møller, L. B. P., Kromann, B., Kabatnik, S., Hjortlund, J. H., Haulrig, M. B., Sølberg, J. B. K., Bzorek, M., Clark, R. A., Skov, L., Mann, M., Løvendorf, M. B., & Dyring-Andersen, B.
ORCID
Dyring-Andersen, Beatrice
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
2025-12
Volume
145
Issue
12
Pages
3051-3063.e2
ISSN
0022-202X
DOI
10.1016/j.jid.2025.05.002
Cited by
12
References
2
Language
en
Licence
Funders
  • Novo Nordisk Foundation (NNF21OC0066694)
  • Max-Planck-Gesellschaft (NNF20SA0035590)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review