2. Academic Validation
  3. Nervonic acid mitigates IMQ-triggered psoriasis in mice via inhibiting Th17/γδT17 cell invasion and modulating the gut microbiota

Nervonic acid mitigates IMQ-triggered psoriasis in mice via inhibiting Th17/γδT17 cell invasion and modulating the gut microbiota

  • J Leukoc Biol. 2025 Jun 4;117(6):qiaf070. doi: 10.1093/jleuko/qiaf070.
Zishan Yang 1 2,  Xiaorong Geng 1,  Shenglan Zhang 1,  Junjie Gao 1,  Fengxiang Ji 1,  Yixuan Han 1,  Zhihao Cui 1,  Xia Wang 2,  Sheng Guo 1,  Dong Yan 1,  Tiesuo Zhao 1,  Feng Ren 2 3,  Xueshi Li 4,  Jie Dong 5,  Zhongwei Tian 6,  Zhinan Yin 7 8,  Xiangfeng Song 1
Affiliations

Affiliations

  • 1 Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, Henan 453003, PR China.
  • 2 Henan Research Center for Engineering Technology in Digestive Tract Tumor Immune Digital Decoding and Cell Therapy, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, Henan 453000, PR China.
  • 3 Henan International Joint Laboratory of Immunity and Targeted Therapy for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang, 601 Jinsui Avenue, Henan 453000, PR China.
  • 4 Department of Orthopedic Surgery, the First Affiliated Hospital, Jinan University, 613 West Huangpu Avenue, Guangzhou 510632, China.
  • 5 Department of Clinical Laboratory, Guangzhou Twelfth People's Hospital, No. 1 Tianqiang Road, Guangzhou 510620, China.
  • 6 Department of Dermatology, the First Affiliated Hospital of Xinxiang Medical University, 88 Jiankang Road Weihui, Henan 453003, PR China.
  • 7 The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, 613 West Huangpu Avenue, Guangzhou, Guangdong 510632, PR China.
  • 8 Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital of Jinan University, 892 East Ring Road, Heyuan 517000, China.
PMID: 40397706 DOI: 10.1093/jleuko/qiaf070
Abstract

Psoriasis is a persistent immune-mediated inflammatory dermatosis. The treatment of psoriasis now features natural medicine as an effective new alternative because of its notable effectiveness and few side effects. Nervonic acid (NA), a long-chain fatty acid mostly sourced from the seed oils of some wild Plants, exhibits significant antidepressant and anti-inflammatory properties. Nonetheless, the pathogenic effects and mechanism of NA in the pathogenesis of psoriasis are unreported. This work demonstrated that NA markedly mitigated IMQ-triggered psoriasis-like skin inflammation and reduced the mRNA expression levels of chemokines (Cxcl1 and Ccl20) and inflammatory factors (S100a8, S100a9, IL-17, and IL-6) both in vitro and in vivo. Mechanistically, NA blocked the IL-17/IMQ-induced NF-κB and p38MAPK signaling pathways in keratinocytes or tissue lesions, downregulated Ccl20 production, and therefore disrupted positive inflammatory feedback by diminishing Th17 or γδT17 cell infiltration. Furthermore, 16s rRNA Sequencing demonstrated that NA therapy significantly elevated the relative abundance of Bacteroidota, but the outcome for Mucispirillum was contrary within the gut microbiota. These bacteria are linked to the onset of psoriasis and inflammation, perhaps contributing to the alleviation of IMQ-induced lesions in mice. In conclusion, NA may alleviate dermatitis in psoriatic mice by inhibiting Th17/γδT17 cell invasion and modulating the gut microbiota. Consequently, NA stands as a highly promising choice for psoriasis treatment.

Keywords

MAPK signaling pathway; NF-κB signaling pathway; gut microbiota; nervonic acid; psoriasis.

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