Myeloid-derived suppressor cells are key elements for symptom recovery in a murine model of multiple sclerosis

Abstract

Microglia are the resident macrophage population of the central nervous system (CNS). In contrast to most other populations of the mononuclear phagocyte system, adult microglia derive from primitive myeloid progenitors that arise in the yolk sac early during embryonic development. In the steady state, microglia maintain themselves locally and independently of circulating bone marrow derived precursors. By comparing the transcriptome of microglia to other tissue macrophage populations we identified Sall1, a gene which codes for a transcription factor and represents a promising candidate to achieve microglia-specific targeting. We could show that of all hematopoietic cells, Sall1 is expressed exclusively bymicroglia. During embryogenesis, Sall1 is not expressed on primitive yolk sac macrophages but microglia precursors in the developing CNS start to express Sall1 from E14.5 and continue to express it throughout life. Even though Sall1 is highly expressed by all microglia, we demonstrated that Sall1 is neither crucial for microglia development and homeostasis nor for their activation in neuro-inflammation. Additionally myeloid cells infiltrating the CNS during neuro-inflammatory conditions do no acquire Sall1 expression indicating that Sall1 expression is unique to microglia and that Sall1Cre mice can be utilized for microglia specific gene-targeting without undesirable targeting of other myeloid cells.