2. Academic Validation
  3. Targeting formyl peptide receptor 2 to suppress neuroinflammation in neuromyelitis optica spectrum disorder

Targeting formyl peptide receptor 2 to suppress neuroinflammation in neuromyelitis optica spectrum disorder

  • Theranostics. 2025 Mar 19;15(10):4495-4506. doi: 10.7150/thno.107303.
Caiyun Qi 1 2,  Hongying Hao 2,  Wei Zhang 1,  Yiwei Fu 2,  Yali Han 2,  Jinyi Li 2,  Lixiang Chen 2,  Guiyun Cui 1,  Qing Liu 3,  Yuan Li 4,  Xiaozhen Wang 4,  Ming-Wei Wang 4 5 6 7,  Qiang Liu 1 2
Affiliations

Affiliations

  • 1 Department of Neurology, Parkinson's Disease Center, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 2 Department of Neurology, Tianjin Neurological Institute, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Ministry of Education, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • 3 The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 4 Research Center for Deepsea Bioresources, Sanya 572025, China.
  • 5 Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
  • 6 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.
  • 7 Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou 570228, China.
PMID: 40225578 DOI: 10.7150/thno.107303
Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated neurological inflammatory disease. As a G protein-coupled receptor, formyl peptide receptor 2 (FPR2) orchestrates innate and adaptive immunity. Yet the precise role of FPR2 in neuroinflammation is poorly understood. Methods: Peripheral blood samples were collected from patients with NMOSD and healthy controls. Single-cell RNA Sequencing (scRNA-seq) and flow cytometry were employed to assess the expression of FPR2 in immune cell subsets. We used a mouse model of NMOSD to examine the therapeutic potential and underlying immune mechanisms of an FPR2 antagonist Quin-C7. MRI and immunostaining were performed to quantify central nervous system injury. Results: ScRNA-seq and flow cytometry analyses revealed that FPR2 was expressed in various myeloid and lymphoid cell types in patients with NMOSD and a mouse model of NMOSD. In NMOSD mice, mouse formyl peptide receptor 2 (mFpr2) was mainly upregulated in microglia. Administration of Quin-C7 led to reduced brain lesion volume, astrocyte loss and demyelination in NMOSD mice. Further, FPR2 antagonism reduced the inflammatory activity of microglia and lymphocyte infiltration into the brain. Notably, depletion of microglia using a CSF1R inhibitor diminished the protective effects of FPR2 antagonism, suggesting that microglia contribute to the benefit of FPR2 antagonism in NMOSD. In contrast, genetic deficiency of T and B cells or antibody depletion of NK cells did not affect the benefit of FPR2 antagonism. Conclusion: Collectively, our findings revealed a previously unrecognized role of FPR2/mFpr2 in control of microglia activity during neuroinflammation, implying that FPR2 antagonism may serve as a viable therapeutic approach to restrict detrimental neuroinflammation and warrant further investigation.

Keywords

FPR2/mFpr2; demyelination; neuroinflammation; neuromyelitis optica spectrum disorder.

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