Transmembrane protein 119 is neither a specific nor a reliable marker for microglia
Elise Vankriekelsvenne1, Uta Chrzanowski1,2, Katerina Manzhula1
1Rostock University Medical Center, Institute of Anatomy, Rostock, Germany.
Abstract:
Microglia are the resident innate immune cells of the central nervous system (CNS) parenchyma. To determine the impact of microglia on disease development and progression in neurodegenerative and neuroinflammatory diseases, it is essential to distinguish microglia from peripheral macrophages/monocytes, which are eventually equally recruited. It has been suggested that transmembrane protein 119 (TMEM119) serves as a reliable microglia marker that discriminates resident microglia from blood-derived macrophages in the human and murine brain. Here, we investigated the validity of TMEM119 as a microglia marker in four in vivo models (cuprizone intoxication, experimental autoimmune encephalomyelitis (EAE), permanent filament middle cerebral artery occlusion (fMCAo), and intracerebral 6-hydroxydopamine (6-OHDA) injections) as well as post mortem multiple sclerosis (MS) brain tissues. In all applied animal models and post mortem MS tissues, we found increased densities of ionized calcium-binding adapter molecule 1+ (IBA1+ ) cells, paralleled by a significant decrease in TMEM119 expression. In addition, other cell types in peripheral tissues (i.e., follicular dendritic cells and brown adipose tissue) were also found to express TMEM119. In summary, this study demonstrates that TMEM119 is not exclusively expressed by microglia nor does it label all microglia, especially under cellular stress conditions. Since novel transgenic lines have been developed to label microglia using the TMEM119 promotor, downregulation of TMEM119 expression might interfere with the results and should, thus, be considered when working with these transgenic mouse models.
Insights
Transmembrane protein 119 (TMEM119) is not a reliable marker for microglia in the central nervous system (CNS). Its expression decreases under disease conditions and it is found in other cell types, impacting research using TMEM119-based models.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Neuroinflammation Research
Background:
- Microglia are crucial innate immune cells in the central nervous system (CNS).
- Distinguishing microglia from infiltrating peripheral macrophages is vital for understanding neurodegenerative and neuroinflammatory diseases.
- Transmembrane protein 119 (TMEM119) has been proposed as a specific marker for microglia in the brain.
Purpose of the Study:
- To evaluate the reliability of TMEM119 as a specific microglia marker in various in vivo disease models and post-mortem human brain tissue.
- To assess TMEM119 expression patterns under conditions of neuroinflammation and neurodegeneration.
Main Methods:
- Investigated TMEM119 expression in four distinct in vivo models: cuprizone intoxication, experimental autoimmune encephalomyelitis (EAE), permanent filament middle cerebral artery occlusion (fMCAo), and intracerebral 6-hydroxydopamine (6-OHDA) injections.
- Analyzed TMEM119 expression in post-mortem multiple sclerosis (MS) brain tissues.
- Examined TMEM119 expression in peripheral cell types, including follicular dendritic cells and brown adipose tissue.
Main Results:
- A significant decrease in TMEM119 expression was observed in ionized calcium-binding adapter molecule 1-positive (IBA1+) cells across all tested animal models and MS tissues.
- TMEM119 was also detected in non-microglial cell types in peripheral tissues.
- These findings indicate that TMEM119 is not exclusively expressed by microglia and its expression is downregulated under cellular stress.
Conclusions:
- TMEM119 is not a universally reliable marker for microglia, particularly under disease or cellular stress conditions.
- The observed downregulation of TMEM119 in microglia may affect the interpretation of studies using TMEM119-based transgenic models.
- Caution is advised when utilizing TMEM119 for microglia identification in research, especially with novel transgenic lines.
