Tmem119 expression is downregulated in a subset of brain metastasis-associated microglia
Weili Ma1, Jack Oswald2, Angela Rios Angulo2
1Immunology, Metastasis and Microenvironment Program, The Wistar Institute, 3601 Spruce Street, 19104, Philadelphia, PA, USA. wma@wistar.org.
Abstract:
Under pathological conditions, the immune-specialized brain microenvironment contains both resident microglia and bone marrow-derived myeloid cells recruited from peripheral circulation. Due to largely overlapping phenotypic similarities between these ontogenically distinct myeloid populations, studying their individual functions in central nervous system diseases has been challenging. Recently, transmembrane protein 119 (Tmem119) has been reported as a marker for resident microglia which is not expressed by bone marrow-derived myeloid cells. However, several studies have reported the loss or reduction of Tmem119 expression in pathologically activated microglia. Here, we examined whether Tmem119 could be used as a robust marker to identify brain metastasis-associated microglia. In addition, we also compared Tmem119 expression of primary microglia to the immortalized microglia-like BV2 cell line and characterized expression changes after LPS treatment. Lastly, we used a commercially available transgenic mouse line (Tmem119-eGFP) to compare Tmem119 expression patterns to the traditional antibody-based detection methods. Our results indicate that brain metastasis-associated microglia have reduced Tmem119 gene and protein expression.
Insights
Transmembrane protein 119 (Tmem119) is a microglial marker, but its expression decreases in brain metastasis. This study investigates Tmem119's reliability in identifying brain metastasis-associated microglia.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- The brain's immune microenvironment involves resident microglia and infiltrating myeloid cells.
- Distinguishing these cell types is crucial for understanding central nervous system diseases.
- Transmembrane protein 119 (Tmem119) was proposed as a specific microglial marker, but its expression can be altered in pathological conditions.
Purpose of the Study:
- To evaluate Tmem119 as a reliable marker for brain metastasis-associated microglia.
- To compare Tmem119 expression in primary microglia versus the BV2 cell line.
- To analyze Tmem119 expression changes following LPS treatment and in a Tmem119-eGFP transgenic mouse model.
Main Methods:
- Investigated Tmem119 gene and protein expression in brain metastasis models.
- Compared primary microglia and BV2 cell line Tmem119 expression.
- Analyzed Tmem119 expression after lipopolysaccharide (LPS) stimulation.
- Utilized a Tmem119-eGFP transgenic mouse line for comparative analysis.
Main Results:
- Brain metastasis-associated microglia exhibit reduced Tmem119 gene and protein expression.
- Tmem119 expression patterns were compared between antibody-based detection and transgenic models.
- LPS treatment effects on Tmem119 expression in microglia were characterized.
Conclusions:
- Tmem119 expression is significantly reduced in brain metastasis-associated microglia.
- Tmem119 may not be a universally robust marker for activated microglia in all pathological contexts.
- Further research is needed to refine markers for distinct myeloid populations in CNS diseases.
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