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Published on: December 26, 2017
Chimeric IL-6/4R-LL37 Engineered Macrophages Achieve Synchronized Inflammation Control and Antimicrobial Defence in
Tianyang Jie1, Zheyu Zhang1, Hao Zhang1
1Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 7, 2026
Summary
This study presents an engineered macrophage therapy for sepsis, utilizing lipid nanoparticles to deliver therapeutic proteins and mRNA. This approach effectively controls infection, reduces inflammation, and restores immune function, significantly improving survival rates in mouse models.
Area of Science:
- Immunology
- Biotechnology
- Pharmacology
Background:
- Sepsis involves complex immune dysregulation, including cytokine storms and persistent immune dysfunction like T cell exhaustion.
- Current treatments manage infection and inflammation but don't resolve T cell exhaustion, a key factor in poor sepsis survival.
- There is a critical need for therapies that address both infection and immune reconstitution in sepsis.
Purpose of the Study:
- To develop and evaluate a multifunctional engineered macrophage strategy for precision sepsis treatment.
- To assess the efficacy of in situ LNP delivery of IL-6/4 fusion protein and LL37 antimicrobial peptide mRNA in engineered macrophages.
- To investigate the impact of this therapy on immune dysregulation, organ damage, and survival in sepsis models.
Main Methods:
- Engineered macrophages were developed using in situ lipid nanoparticle (LNP) delivery of IL-6/4 fusion protein and LL37 antimicrobial peptide mRNA.
- The therapeutic effects were evaluated in established sepsis mouse models.
- Key outcomes measured included survival rates, histopathological damage, bacterial burden, and immune cell function (T cells and macrophages).
Main Results:
- Engineered macrophages significantly improved survival rates in sepsis mouse models.
- The therapy effectively reduced histopathological damage and bacterial burden in organs.
- Restoration of T cell and macrophage functions was observed, indicating successful immune reconstitution.
- The combined approach achieved infection control, inflammation modulation, and immune recovery.
Conclusions:
- Engineered macrophages represent a promising multifunctional therapeutic strategy for sepsis.
- This approach effectively addresses critical aspects of sepsis pathology, including infection, inflammation, and immune dysfunction.
- The findings highlight the substantial clinical translational potential of this precision medicine approach for sepsis treatment.
