Autoimmune neurologic diseases
Microglia, the resident immune cells in the central nervous system (CNS), play a critical role in the pathogenesis of neurodegenerative diseases including multiple sclerosis (MS). Although microglia are thought to contribute to the inflammatory component of neurodegeneration and axonal loss in MS, the relationship between MS progression and inflammation in the brain remains ambiguous because microglia and monocyte-derived macrophages are difficult to distinguish from one another in an inflamed brain. Transmembrane protein 119 (TMEM119) is a microglia-specific marker, and because it has no reported expression in macrophages or other immune cells, can be useful for discriminating resident microglia from any infiltrating macrophages in inflamed CNS tissues. Here, we characterized a new reporter mouse model, which contains a tdTomato reporter transgene linked to TMEM119 (knockin). By tracking the fluorescence of tdTomato, we can track and isolate the TMEM119-expressed microglia. Our immunostaining in brain sections showed that all tdTomato+ cells express Iba1 in both neurocortex and hippocampus, while a small amount of Iba1+ cells did not express tdTomato, particularly in the hippocampus. Using two-photon microscope in experimental autoimmune encephalomyelitis (EAE) mice, we found that microglia differentiate into an activated phenotype revealed by a rounded shape and are recruited to inflammatory sites in the spinal cord, and form synapses with adoptively transferred regulatory CD4+Foxp3/GFP+ T cells (Tregs). Overall, our model is a valuable tool to study the function of microglia compared to infiltrating macrophages and their crosstalk with pro-inflammatory and regulatory T cells.