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Updated: Nov 26, 2025
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis
Elien Wouters1, Elien Grajchen1, Winde Jorissen1
1Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, Belgium.
Abstract:
Macrophages play a crucial role during the pathogenesis of multiple sclerosis (MS), a neuroinflammatory autoimmune disorder of the central nervous system. Important regulators of the metabolic and inflammatory phenotype of macrophages are liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs). Previously, it has been reported that PPARγ expression is decreased in peripheral blood mononuclear cells of MS patients. The goal of the present study was to determine to what extent PPARγ, as well as the closely related nuclear receptors PPARα and β and LXRα and β, are differentially expressed in monocytes from MS patients and how this change in expression affects the function of monocyte-derived macrophages. We demonstrate that monocytes of relapsing-remitting MS patients display a marked decrease in PPARγ expression, while the expression of PPARα and LXRα/β is not altered. Interestingly, exposure of monocyte-derived macrophages from healthy donors to MS-associated proinflammatory cytokines mimicked this reduction in PPARγ expression. While a reduced PPARγ expression did not affect the inflammatory and phagocytic properties of myelin-loaded macrophages, it did impact myelin processing by increasing the intracellular cholesterol load of myelin-phagocytosing macrophages. Collectively, our findings indicate that an inflammation-induced reduction in PPARγ expression promotes myelin-induced foam cell formation in macrophages in MS.
Insights
Multiple sclerosis (MS) macrophages show reduced PPARγ expression, impacting myelin processing and increasing cholesterol. This inflammation-driven decrease promotes foam cell formation in MS.
Area of Science:
- Neuroimmunology
- Cellular Metabolism
- Autoimmune Disorders
Background:
- Macrophages are key players in multiple sclerosis (MS) pathogenesis.
- Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) regulate macrophage function.
- Previous studies indicated decreased PPARγ in MS patients' peripheral blood cells.
Purpose of the Study:
- To investigate differential expression of PPARγ, PPARα/β, and LXRα/β in monocytes from MS patients.
- To determine how altered expression affects monocyte-derived macrophage function.
- To explore the role of PPARγ in myelin processing and cholesterol accumulation in MS macrophages.
Main Methods:
- Monocyte isolation from relapsing-remitting MS patients and healthy donors.
- Quantitative analysis of nuclear receptor gene expression (PPARγ, PPARα/β, LXRα/β).
- Functional assays on monocyte-derived macrophages, including inflammatory and phagocytic properties, and myelin processing.
Main Results:
- Monocytes from MS patients exhibited significantly reduced PPARγ expression.
- PPARα and LXRα/β expression remained unchanged in MS monocytes.
- Exposure to MS-associated pro-inflammatory cytokines mimicked reduced PPARγ expression in macrophages from healthy donors.
- Reduced PPARγ did not alter inflammatory or phagocytic capacity but increased intracellular cholesterol during myelin processing.
- This suggests inflammation-induced PPARγ reduction promotes myelin-induced foam cell formation.
Conclusions:
- Inflammation in MS leads to decreased PPARγ expression in monocytes.
- Reduced PPARγ impairs myelin processing, causing cholesterol accumulation and foam cell formation in macrophages.
- Targeting PPARγ may offer a therapeutic strategy for MS by modulating macrophage lipid metabolism.
