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Updated: Jun 23, 2026

A Thin-skull Window Technique for Chronic Two-photon In vivo Imaging of Murine Microglia in Models of Neuroinflammation
Published on: September 19, 2010
TIAM2S-positive microglia enhance inflammation and neurotoxicity through soluble ICAM-1-mediated immune priming
Chun-Hsien Chu1,2, Jia-Shing Chen3, Ya-Ling Chan4
1Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Abstract:
TIAM Rac1-associated GEF 2 short form (TIAM2S) as an oncoprotein alters the immunity of peripheral immune cells to construct an inflammatory tumor microenvironment. However, its role in the activation of microglia, the primary innate immune cells of the brain, and neuroinflammation remains unknown. This study investigated the mechanism underlying TIAM2S shapes immune properties of microglia to facilitate neuron damage. Human microglial clone 3 cell line (HMC3) and human brain samples were applied to determine the presence of TIAM2S in microglia by western blots and double immunostaining. Furthermore, TIAM2S transgenic mice combined with multiple reconstituted primary neuron-glial culture systems and a cytokine array were performed to explore how TIAM2S shaped immune priming of microglia and participated in lipopolysaccharide (LPS)-induced neuron damage. TIAM2S protein was detectable in HMC3 cells and presented in a small portion (~11.1%) of microglia in human brains referred to as TIAM2S-positive microglia. With the property of secreted soluble factor-mediated immune priming, TIAM2S-positive microglia enhanced LPS-induced neuroinflammation and neural damage in vivo and in vitro. The gain- and loss-of-function experiments showed soluble intercellular adhesion molecule-1 (sICAM-1) participated in neurotoxic immune priming of TIAM2S+ microglia. Together, this study demonstrated a novel TIAM2S-positive microglia subpopulation enhances inflammation and neurotoxicity through sICAM-1-mediated immune priming.
Insights
TIAM2S protein in microglia drives brain inflammation and neuron damage. This subpopulation enhances neuroinflammation and neurotoxicity via soluble intercellular adhesion molecule-1, contributing to brain injury.
Area of Science:
- Neuroscience
- Immunology
- Oncology
Background:
- TIAM Rac1-associated GEF 2 short form (TIAM2S) is an oncoprotein affecting peripheral immune cells.
- The role of TIAM2S in microglial activation and brain neuroinflammation is currently unknown.
Purpose of the Study:
- To investigate the mechanism by which TIAM2S influences microglial immune properties.
- To determine TIAM2S's role in shaping microglial immune priming and facilitating neuron damage.
Main Methods:
- Western blots and double immunostaining in HMC3 cells and human brain samples.
- TIAM2S transgenic mice and primary neuron-glial co-culture systems.
- Cytokine array analysis and gain/loss-of-function experiments.
Main Results:
- TIAM2S protein was detected in HMC3 cells and a subset of human microglia (TIAM2S-positive microglia).
- TIAM2S-positive microglia promoted LPS-induced neuroinflammation and neural damage in vitro and in vivo.
- Soluble intercellular adhesion molecule-1 (sICAM-1) was identified as a mediator in TIAM2S+ microglia-induced neurotoxic immune priming.
Conclusions:
- A novel subpopulation of TIAM2S-positive microglia contributes to neuroinflammation and neurotoxicity.
- TIAM2S-positive microglia enhance brain inflammation and neuron damage through sICAM-1-mediated immune priming.
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