Defective neutrophil-derived exosomes facilitate macrophage activation through miR-122-5p in Behçet’s disease
Behçet's disease (BD) is a life-threatening systemic vasculitis characterized by polymorphonuclear neutrophils (PMN) and macrophage activation. However, the interaction of PMN and macrophages remains elusive. To elucidate the potential dysregulation of BD PMN exosomes on macrophage activation, PMN exosomes from both BD patients and healthy controls are isolated, quantified and incubated with macrophages. We find that BD PMN exosomes are decreased and negatively correlated with C-reactive protein (CRP). PMN exosomes can suppress IL-6, TNF, CD80 and CD86 expressions on macrophages, which are attenuated in BD PMN exosomes. In addition, by miRNA sequencing of PMN exosomes, RNA sequencing of miRNA-transfected macrophages, and dual luciferase reporter assay validation of the miRNA target, we find that miR-122-5p is decreased in BD PMN exosomes, targeting IRF5, suppressing TLR4 signaling and IFN-β autocrine, eventually downregulating macrophage activation. Our study illustrates that BD PMN exosomes are decreased in both quantity and miR-122-5p, which impairs the potential immunoregulatory effects on macrophages through degrading IRF5 and suppressing IFN-β autocrine, shedding light on the interaction mechanism between PMN and macrophages.
Authors
- Lidan Zhao (ORCID: https://orcid.org/0000-0001-6599-3339)
- Yiyuan Ao
- Wenjie Zheng (ORCID: https://orcid.org/0000-0002-3165-8185)
- Zhimian Wang
- Yeling Liu
- Xiaoou Wang (ORCID: https://orcid.org/0000-0002-7040-5383)
- Min Shen (ORCID: https://orcid.org/0000-0003-1912-126X)
- Na Kang (ORCID: https://orcid.org/0000-0003-4771-0475)
- Xin Yu (ORCID: https://orcid.org/0000-0001-9964-951X)
- Li Wang (ORCID: https://orcid.org/0000-0002-4706-2482)
- Hua Chen (ORCID: https://orcid.org/0000-0002-0641-2837)
- Lu Li (ORCID: https://orcid.org/0009-0008-1104-8655)
- Chaoran Li (ORCID: https://orcid.org/0000-0003-4079-2164)
- Fengchun Zhang (ORCID: https://orcid.org/0000-0003-0387-1672)
- Jinjing Liu (ORCID: https://orcid.org/0000-0003-2150-7540)
- Yan Zhao (ORCID: https://orcid.org/0000-0002-5843-3816)
- Menghao Zhang (ORCID: https://orcid.org/0009-0002-5481-6390)
Institutions
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking Union Medical College Hospital (CN)
- National Clinical Research Center for Digestive Diseases (CN)
- Peking University Shougang Hospital (CN)
- Center for Life Sciences (CN)
- Tsinghua University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-02
- DOI
- https://doi.org/10.1038/s41467-025-63348-8
- Citations
- 1
- Primary Topic
- Ocular Diseases and Behçet’s Syndrome
- Type
- article
- Field-Weighted Citation Impact
- 1.71
Funders
- National Natural Science Foundation of China
- Peking Union Medical College Hospital
- Peking Union Medical College