Significance Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by accumulation of myeloid cells in the central nervous system (CNS). Both harmful and beneficial myeloid cells are present in EAE/MS, and a goal of MS therapy is to preferentially remove harmful myeloid cells. The receptor for CSF-1 (CSF-1R) is found on myeloid cells and is important for their survival. CSF-1R can bind two ligands, CSF-1 and IL-34, but it is not known whether their functions in EAE/MS differ. We found that blocking CSF-1 depleted only harmful myeloid cells in the CNS and suppressed EAE, whereas blocking IL-34 had no effect. Thus, we propose that blocking CSF-1 could be a therapy for MS.

GATA-binding factor 1 (GATA1) is a transcription factor that governs the development and function of multiple hematopoietic cell lineages. GATA1 is expressed in hematopoietic stem and progenitor cells (HSPCs) and is essential for erythroid lineage commitment, but if and what role it has in hematopoietic stem cell (HSC) biology and in the development of myeloid lineage cells is less clear. We initially set out to test the role of eosinophils in experimental autoimmune encephalomyelitis (EAE), a model of CNS autoimmunity, by using ΔdblGATA mice, which lack eosinophils due to deletion of the dblGATA enhancer to Gata1 that alters its expression. ΔdblGATA mice were resistant to EAE, but not because of the lack of eosinophils, suggesting that these mice have an additional defect. ΔdblGATA mice with EAE had fewer inflammatory myeloid cells than control mice, suggesting that the resistance to EAE is caused by a defect in myeloid cells. Naïve ΔdblGATA mice also had reduced frequency of blood CD11b+ myeloid cells, indicating a defect in myeloid cell production. Examination of HSPCs revealed fewer HSCs and myeloid cell progenitors in ΔdblGATA bone marrow, and competitive bone marrow chimera experiments showed a reduced capacity of ΔdblGATA bone marrow to reconstitute immune cells, suggesting that reduced numbers of ΔdblGATA HSPCs causes a functional deficit during inflammation. Taken together, our data show that GATA1 regulates the number of HSPCs, and that reduced GATA1 expression, due to dblGATA deletion, results in a diminished immune response following inflammatory challenge.