Abstract
Psoriasis patients who are obese tend to have serious clinical manifestations and poor responses to various biological agents in most cases. However, the mechanisms by which obesity exacerbates psoriasis remain enigmatic. In this study, we found that the abundance of systemic and localized cutaneous neutrophil extracellular traps (NETs) associated with the obesity-induced aggravation of psoriasis was positively correlated with disease severity and that the inhibition of NETs alleviated psoriatic dermatitis in obese mice. Mechanistically, we found that changes in fatty acid composition in obese subjects resulted in the deposition of saturated fatty acids (SFAs), which promoted the release of NETs via the TLR4-MD2/ROS signaling pathway. We further revealed that NETs potentiate IL-17 inflammation, especially γδT17-mediated immune responses, in obesity-exacerbated psoriasis patients. Moreover, SFAs induced a decreased response to anti-IL17A treatment in psoriasis-like mice, whereas the inhibition of NETs improved the beneficial effects of anti-IL17A in psoriasis-like mice with lipid metabolism disorders. Our findings collectively suggest that SFA-induced NETs play a critical role in the exacerbation of obesity-related psoriasis and provide potential new strategies for the clinical treatment of refractory psoriasis patients with lipid metabolism disorders.
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Data availability
The data underlying this article will be shared upon reasonable request to the corresponding author.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (82130089, 82103730, 82304022, and 32070894), the Key R&D Program of Hubei Province (YFXM2021000203), the National Key Research and Development Program of China (2020YFA0804400), and the Program of HUST Academic Frontier Youth Team (2018QYTD10). We thank all the members of the Medical Subcenter of the Analytical and Testing Center, Huazhong University of Science and Technology, for their technical assistance. We thank all the members of the Institutional Animal Care and Use Committee, Huazhong University of Science and Technology, for showing loving care for life.
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These authors contributed equally: Yuting Xia, Jiajia Lan.
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Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Yuting Xia, Jiajia Lan, Jing Yang, Hongyao Du, Wenjia Nie, Biling Jiang, Liang Zhao, Zhen Cai, Xin Zhang, Yan Xiong, Yan Li & Juan Tao
Hubei Engineering Research Center of Skin Disease Theranostics and Health, Wuhan, Hubei, China
Yuting Xia, Jiajia Lan, Jing Yang, Hongyao Du, Wenjia Nie, Biling Jiang, Liang Zhao, Zhen Cai, Xin Zhang, Yan Xiong, Yan Li & Juan Tao
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Yuting Xia, Shijie Yuan, Xiaorong Xie, Qiuyang Du & Ran He
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Yuting Xia
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Contributions
Y.X. and J.L. designed the project, performed the experiments, analyzed the data, and wrote the manuscript. S.Y., X.X., Q.D., H.D., W.N., B.J., L.Z., Z.C., X.Z. and Y.X. conducted the experiments. J.Y. and Y.L. interpreted the data. R.H. and J.T. designed the project, oversaw the studies, provided intellectual support, and edited the manuscript. All the authors edited and approved the manuscript.
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Correspondence to Ran He or Juan Tao.
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All studies involving mice were approved by the Institutional Animal Care and Use Committee of Huazhong University of Science and Technology with ethics approval number IACUC- [2022]-3147. All human clinical protocols were approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, with an ethics approval number of EC- [2023]-S053. Written informed consent was obtained from the patients before participation in the study.
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Xia, Y., Lan, J., Yang, J. et al. Saturated fatty acid-induced neutrophil extracellular traps contribute to exacerbation and biologic therapy resistance in obesity-related psoriasis. Cell Mol Immunol (2025). https://doi.org/10.1038/s41423-025-01278-7
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Received:19 August 2024
Accepted:06 March 2025
Published:01 April 2025
DOI:https://doi.org/10.1038/s41423-025-01278-7
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Keywords
neutrophil extracellular traps
psoriasis
saturated fatty acids
anti-IL17A
obesity