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Formyl peptide receptor 2 is a potential biomarker and therapeutic target for inflammatory bowel disease

Acta Pharmacologica Sinica (2025)Cite this article

Abstract

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is characterized by limited treatment options and a therapeutic ceiling. Failure to resolve inflammation is the key driver of disease progression. Formyl peptide receptor 2 (FPR2/ALX), a pivotal mediator of inflammation resolution, has emerged as a promising therapeutic target. In this study, we investigated the expression patterns of FPR2 and clinical relevance in myeloid and lymphoid cells of active IBD patients. By analyzing transcriptomic and single-cell RNA-sequencing data from the GEO database, we revealed aberrant expression of FPR2 and its associated genes in colonic mucosa of IBD patients. We found that FPR2/ALX was highly expressed in the colonic mucosa of UC and CD patients compared to non-IBD controls, strongly correlating with alterations in the MAPK pathway and myeloid cell composition. Notably, high mucosal FPR2/ALX levels were associated with poor response to anti-tumor necrosis factor-α (TNF-α) agent infliximab, and were predictive of disease status (AUC = 0.9143). To assess therapeutic potential, we established a dextran sulfate sodium (DSS)-induced colitis model in wild-type and Fpr2-silenced mice. The mice were orally treated with FPR2/ALX modulators Quin-C1 (QC1) and Quin-C7 (QC7) for 7 days. We showed that oral administration of QC1 or QC7 significantly reduced disease active index (DAI) in wild-type mice, whereas the therapeutic effects were markedly impaired in Fpr2-silenced mice. We conclude that FPR2/ALX may serve as a potential biomarker and therapeutic target for IBD.

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Fig. 1: Elevated expression of FPR2 in the colonic mucosa of IBD patients.
Fig. 2: Gene expression and immune cell composition in the colon of UC patients.
Fig. 3: Gene expression and immune cell composition in the colonic mucosa of CD patients before and after infliximab treatment.
Fig. 4: Correlation between FPR2 and OSM in UC patients.
Fig. 5: Association of FPR2/ALX with anti-TNF-α treatment response.
Fig. 6: Effects of Fpr2 gene silencing on the anti-colitis efficacy of QC1 and QC7.

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Acknowledgements

This work was partially supported by Shanghai Hospital Development Center Foundation SHDC22024204 (ZPL), Shanghai Medicine and Health Development Foundation 20221128 (ZPL), and Shanghai Municipal Human Resources and Social Security Bureau EK00000861 (ZPL); the National Natural Science Foundation of China 82273961 (MWW), 82073904 (MWW), and 81872915 (MWW); STI2030-Major Project 2021ZD0203400 (QTZ) and Hainan Provincial Major Science and Technology Project ZDKJ2021028 (QTZ).

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, China

    Wen-sheng Yang, Wei Wu, Guang-fei Wang & Zhi-ping Li

  2. Research Center for Deepsea Bioresources, Sanya, 572025, China

    Xiao-zhen Wang, Yuan Li, Qing-tong Zhou & Ming-Wei Wang

  3. Research Center for Medicinal Structural Biology, National Research Center for Translational Medicine at Shanghai, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Qing-tong Zhou & Ming-Wei Wang

  4. Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

    Ming-Wei Wang

  5. Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou, 570228, China

    Ming-Wei Wang

  6. Department of Clinical Pharmacy, Kunshan Maternity and Children’s Health Care Hospital, Children’s Hospital of Fudan University, Kunshan Branch, Kunshan, 215300, China

    Zhi-ping Li

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Contributions

WSY, ZPL, and MWW designed research; WSY contributed to methodology; WSY, XZW, and YL performed experiments; WSY, WW, GFW and QTZ analyzed the data; MWW and ZPL supervised the project; WSY, ZPL and MWW wrote the manuscript. All authors have reviewed and approved the manuscript.

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Correspondence to Ming-Wei Wang or Zhi-ping Li.

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Yang, Ws., Wang, Xz., Wu, W. et al. Formyl peptide receptor 2 is a potential biomarker and therapeutic target for inflammatory bowel disease. Acta Pharmacol Sin (2025). https://doi.org/10.1038/s41401-025-01695-4

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