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Peer-reviewedCC BY 4.0European Journal of Immunology

Prophylactic Soraphen A Treatment Attenuates Western Diet‐Exacerbated IMQ‐Induced Psoriasiform Inflammation

  • Yu‐San Kao1
  • Katharina S. Kommoss2,3
  • Tabea Bieler2,4
  • Gloria Janet Godoy5
  • Aleksandra Lopez Krol1
  • Fatima Boukhallouk1
  • Felix K. F. Kommoss6
  • Danijela Heide2
  • Susanne H. Kirsch7,8
  • Rolf Müller7,8,9
  • Mathias Heikenwälder2,10
  • Tim Sparwasser1,11
11 affiliations
  1. 1Institute of Medical Microbiology and Hygiene University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
  2. 2Division of Chronic Inflammation and Cancer German Cancer Research Center (DKFZ) Heidelberg Germany
  3. 3Department of Dermatology University Hospital Heidelberg Heidelberg Germany
  4. 4Fachbereich Biologie Johannes Gutenberg University Mainz Mainz Germany
  5. 5Institute of Molecular Medicine University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
  6. 6Institute of Pathology University Hospital Heidelberg Heidelberg Germany
  7. 7Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) Helmholtz Centre for Infection Research (HZI) Saarland University Campus Saarbrücken Germany
  8. 8German Centre for Infection Research (DZIF) Partner Site Hannover‐Braunschweig Braunschweig Germany
  9. 9Department of Pharmacy Saarland University Saarbrücken Germany
  10. 10The M3 Research Center Institute For Interdisciplinary Research On Cancer Metabolism and Chronic Inflammation Eberhard Karls University Tübingen Medical Faculty Tübingen Germany
  11. 11Research Center for Immunotherapy (FZI) University Medical Center Johannes Gutenberg‐University Mainz Mainz Germany
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Abstract

Psoriasis is a T‐cell‐mediated inflammatory disease amplified by metabolic stress. Acetyl‐CoA carboxylase 1 (ACC1)‐dependent fatty acid synthesis is required for IL‐17‐producing T cells. Here, we asked whether short‐term systemic administration of soraphen A (SorA), a dual ACC1/2 inhibitor, modulates imiquimod (IMQ)‐induced psoriasiform inflammation under normal diet (ND) and Western diet (WD) conditions. Female C57BL/6J mice were fed ND or WD for 12 weeks prior to daily intraperitoneal injections of SorA or vehicle for 10 days, followed by 5 days of topical IMQ to induce psoriasiform dermatitis. Disease severity was assessed by macroscopic, histological, transcriptional, and flow cytometric readouts. Prophylactic SorA administration had no measurable effect in ND‐fed mice. In WD‐fed mice, prophylactic SorA reduced erythema, back skin thickening, and epidermal hyperplasia, whereas scaling remained unchanged. Selected histological skin readouts were numerically lower, whereas the qPCR panel showed no statistically significant differences. In skin‐draining lymph nodes, IL‐17A+ CD4+ and CD8+ T‐cell frequencies and numbers were significantly reduced, whereas γδT17 cells did not differ significantly. Hepatic steatosis scores were unchanged, but hepatic neutrophil infiltration was reduced. Under the present prophylactic regimen, systemic SorA administration was associated with modest attenuation of WD‐exacerbated IMQ‐induced psoriasiform inflammation. These findings support further preclinical evaluation of ACC‐targeted immunometabolic interventions in metabolically aggravated psoriasiform inflammation.

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Cite

BibTeXRIS
BibTeX
@article{kao2026prophylactic,
  title = {{Prophylactic Soraphen A Treatment Attenuates Western Diet‐Exacerbated IMQ‐Induced Psoriasiform Inflammation}},
  author = {Yu‐San Kao and Katharina S. Kommoss and Tabea Bieler and Gloria Janet Godoy and Aleksandra Lopez Krol and Fatima Boukhallouk and Felix K. F. Kommoss and Danijela Heide and Susanne H. Kirsch and Rolf Müller and Mathias Heikenwälder and Tim Sparwasser},
  journal = {European Journal of Immunology},
  year = {2026},
  month = oct,
  doi = {10.1002/eji.70298},
  url = {https://doi.org/10.1002/eji.70298},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Prophylactic Soraphen A Treatment Attenuates Western Diet‐Exacerbated IMQ‐Induced Psoriasiform Inflammation
AU  - Yu‐San Kao
AU  - Katharina S. Kommoss
AU  - Tabea Bieler
AU  - Gloria Janet Godoy
AU  - Aleksandra Lopez Krol
AU  - Fatima Boukhallouk
AU  - Felix K. F. Kommoss
AU  - Danijela Heide
AU  - Susanne H. Kirsch
AU  - Rolf Müller
AU  - Mathias Heikenwälder
AU  - Tim Sparwasser
PY  - 2026
DA  - 2026/10/27
JO  - European Journal of Immunology
DO  - 10.1002/eji.70298
UR  - https://doi.org/10.1002/eji.70298
AB  - Psoriasis is a T‐cell‐mediated inflammatory disease amplified by metabolic stress. Acetyl‐CoA carboxylase 1 (ACC1)‐dependent fatty acid synthesis is required for IL‐17‐producing T cells. Here, we asked whether short‐term systemic administration of soraphen A (SorA), a dual ACC1/2 inhibitor, modulates imiquimod (IMQ)‐induced psoriasiform inflammation under normal diet (ND) and Western diet (WD) conditions. Female C57BL/6J mice were fed ND or WD for 12 weeks prior to daily intraperitoneal injections of SorA or vehicle for 10 days, followed by 5 days of topical IMQ to induce psoriasiform dermatitis. Disease severity was assessed by macroscopic, histological, transcriptional, and flow cytometric readouts. Prophylactic SorA administration had no measurable effect in ND‐fed mice. In WD‐fed mice, prophylactic SorA reduced erythema, back skin thickening, and epidermal hyperplasia, whereas scaling remained unchanged. Selected histological skin readouts were numerically lower, whereas the qPCR panel showed no statistically significant differences. In skin‐draining lymph nodes, IL‐17A+ CD4+ and CD8+ T‐cell frequencies and numbers were significantly reduced, whereas γδT17 cells did not differ significantly. Hepatic steatosis scores were unchanged, but hepatic neutrophil infiltration was reduced. Under the present prophylactic regimen, systemic SorA administration was associated with modest attenuation of WD‐exacerbated IMQ‐induced psoriasiform inflammation. These findings support further preclinical evaluation of ACC‐targeted immunometabolic interventions in metabolically aggravated psoriasiform inflammation.
SN  - 0014-2980
SN  - 1521-4141
ER  -