2. Academic Validation
  3. Regulatory Fibroblast-Like Synoviocytes Cell Membrane Coated Nanoparticles: A Novel Targeted Therapy for Rheumatoid Arthritis

Regulatory Fibroblast-Like Synoviocytes Cell Membrane Coated Nanoparticles: A Novel Targeted Therapy for Rheumatoid Arthritis

  • Adv Sci (Weinh). 2022 Dec 12;e2204998. doi: 10.1002/advs.202204998.
Yuan Liu 1 2 3,  Peishi Rao 1 2 4,  Hongyan Qian 1 2 3,  Yesi Shi 3,  Shiju Chen 1 2 3,  Jingying Lan 1 2,  Dan Mu 3,  Rongjuan Chen 1 2,  Xinwei Zhang 1 2 3,  Chaoqiong Deng 1 2,  Gang Liu 3,  Guixiu Shi 1 2 3
Affiliations

Affiliations

  • 1 Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Xiamen University, Xiamen, 361001, China.
  • 2 School of Medicine, Xiamen University, Xiamen, 361103, China.
  • 3 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen, 361001, China.
  • 4 Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China.
PMID: 36509660 DOI: 10.1002/advs.202204998
Abstract

Fibroblast-like synoviocytes (FLS) are the main cell component in the inflamed joints of patients with rheumatoid arthritis (RA). FLS intimately interact with infiltrating T cells. Fibroblasts have potent inhibitory effects on T cells, leading to the resolution of inflammation and immune tolerance. However, this "regulatory" phenotype is defect in RA, and FLS in RA instead act as "proinflammatory" phenotype mediating inflammation perpetuation. Signals that orchestrate fibroblast heterogeneity remain unclear. Here, it is demonstrated that different cytokines can induce distinct phenotypes of FLS. Interferon-gamma (IFN-γ) is pivotal in inducing the regulatory phenotype of FLS (which is termed FLSreg ) characterized by high expressions of several inhibitory molecules. Rapamycin enhances the effect of IFN-γ on FLS. Based on the characteristics of FLSreg , a novel biomimetic therapeutic strategy for RA is designed by coating cell membrane derived from FLSreg induced by IFN-γ and rapamycin on nanoparticles, which is called FIRN. FIRN show good efficacy, stability, and inflammatory joint targeting ability in an RA mouse model. The findings clarify how fibroblast phenotypes are modulated in the inflammatory microenvironment and provide insights into novel therapeutic designs for autoimmune diseases based on regulatory fibroblasts.

Keywords

cell membrane coated nanoparticle; regulatory fibroblast; rheumatoid arthritis.

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