IGF-2 Preprograms Maturing Macrophages to Acquire Oxidative Phosphorylation-Dependent Anti-inflammatory Properties
Liming Du1, Liangyu Lin1, Qing Li2
1Shanghai Jiao Tong University School of Medicine and Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China; The First Affiliated Hospital of Soochow University and State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123, China.
Cell Metabolism
|February 13, 2019
Summary
Scientists discovered that insulin-like growth factor 2 (IGF-2) trains macrophages to fight inflammation. This reprogramming enhances oxidative phosphorylation (OXPHOS) and boosts anti-inflammatory responses, offering a new strategy for autoimmune disease treatment.
Area of Science:
- Immunology
- Cell Biology
- Metabolic Regulation
Background:
- Macrophages play a key role in immune responses and can be modulated for therapeutic benefit.
- Experimental autoimmune encephalomyelitis (EAE) is a model for studying autoimmune diseases like multiple sclerosis.
- Mesenchymal stem cells have shown potential in treating inflammatory conditions.
Purpose of the Study:
- To investigate the role of insulin-like growth factor 2 (IGF-2) in modulating macrophage function.
- To determine if IGF-2 can induce anti-inflammatory properties in macrophages.
- To evaluate the therapeutic potential of IGF-2-trained macrophages in experimental autoimmune encephalomyelitis (EAE).
Main Methods:
- Investigating the effect of mesenchymal stem cells on EAE in mice.
- Analyzing the impact of IGF-2 on macrophage maturation and metabolic programming.
- Assessing oxidative phosphorylation (OXPHOS) and programmed death-ligand 1 (PD-L1) expression in macrophages.
- Evaluating the therapeutic efficacy of IGF-2-preprogrammed macrophages via adoptive transfer in EAE models.
Main Results:
- IGF-2 critically trains maturing macrophages to adopt an anti-inflammatory phenotype.
- IGF-2 preprogramming commits macrophages to oxidative phosphorylation (OXPHOS), maintaining mitochondrial function under inflammatory conditions.
- IGF-2-trained macrophages exhibit elevated programmed death-ligand 1 (PD-L1) expression, crucial for their anti-inflammatory effects.
- Adoptive transfer of IGF-2-preprogrammed macrophages increased regulatory T cells (Tregs) and alleviated EAE symptoms.
Conclusions:
- IGF-2 is a key mediator in programming macrophages for anti-inflammatory functions.
- Committing macrophages to OXPHOS is a viable strategy to establish their anti-inflammatory fate.
- IGF-2-mediated macrophage reprogramming offers a promising therapeutic avenue for managing inflammatory and autoimmune diseases.
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