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Updated: Jul 14, 2026
Engineering of Human Blood-Induced Microglia-like Cells for Reverse-Translational Brain Research
Published on: September 6, 2024
Microglia can be induced by IFN-gamma or IL-4 to express neural or dendritic-like markers
Oleg Butovsky1, Shay Bukshpan, Gilad Kunis
1Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel.
Abstract:
Microglia are resident cells in the central nervous system (CNS), of hematopoietic origin with a high plasticity. In this study, we examined whether adaptive immune system, involving in CNS maintenance and repair, can induce microglia to express markers of neural cells. We show that long exposure (above 10 days) of microglia to low doses (10 ng/ml) of the 'proinflammatory' T-cell derived cytokine, IFN-gamma, induced them to express neuronal markers including gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD-67). In contrast, exposure of microglia to low doses (10 ng/ml) of the 'anti-inflammatory' T-cell derived cytokine, IL-4, induced the expression of oligodendrocyte markers and dendritic cell (DC) marker, CD11c. The microglial origin of the neural-like cells was confirmed using microglia from transgenic mice expressing GFP under promoter of the chemokine fractalkine receptor CX(3)CR1, and diphtheria toxin receptor, under CD11c promoter. This study emphasizes that microglial plasticity includes their ability to give rise to neural-like cells and shows that cytokines produced by the adaptive immune system are involved in these processes.
Insights
Adaptive immune system cytokines can transform microglia into neural-like cells. Interferon-gamma (IFN-γ) induces neuronal markers, while Interleukin-4 (IL-4) promotes oligodendrocyte and dendritic cell markers in microglia.
Area of Science:
- Neuroimmunology
- Cellular plasticity
- Central nervous system (CNS) research
Background:
- Microglia are hematopoietic-derived resident immune cells in the CNS.
- Microglia exhibit significant plasticity and play roles in CNS maintenance and repair.
- The influence of the adaptive immune system on microglial differentiation is not fully understood.
Purpose of the Study:
- To investigate if adaptive immune system components can induce microglia to express neural cell markers.
- To determine the effects of specific T-cell derived cytokines on microglial differentiation.
- To confirm the microglial origin of induced neural-like cells.
Main Methods:
- Long-term exposure of primary microglia to low doses of IFN-γ or IL-4.
- Analysis of microglial marker expression, including neuronal (GABA, GAD-67) and oligodendrocyte markers.
- Utilizing transgenic mice (CX3CR1-GFP, CD11c-DTR) to trace microglial lineage.
Main Results:
- Exposure to IFN-γ induced neuronal markers (GABA, GAD-67) in microglia.
- Exposure to IL-4 induced oligodendrocyte markers and the dendritic cell marker CD11c in microglia.
- Transgenic mouse models confirmed the neural-like cells originated from microglia.
Conclusions:
- Microglial plasticity extends to the generation of neural-like cells.
- Cytokines from the adaptive immune system, specifically IFN-γ and IL-4, direct microglial differentiation into distinct neural phenotypes.
- This highlights a novel mechanism for CNS cell modulation by immune signals.
