Expression of Olig2 by terminally differentiated eosinophils: its functional implication

Abstract

Olig2, a basic helix loop helix transcription factor, plays a key role in determining specification of oligodendrocytes and motor neurons. Eosinophil is a granulocyte that plays roles in homeostasis and in the pathophysiology of allergic diseases and helminth infection. In the present study, Olig2 is identified as a gene that is exclusively expressed in eosinophils and potentially regulates immune functions of eosinophils. When human cord blood (CB) CD34+ hematopoietic stem cells differentiated toward eosinophils during a culture period of 24 days, Olig2 protein was essentially expressed at the very terminal stage of differentiation. In agreement, it was expressed in eosinophilic and mast cell lines but not in monocytic and lymphocytic cell lines and importantly enough, it was also abundantly expressed in eosinophils, but not in neutrophils or mononuclear cells from peripheral blood. In vitro reporter plasmid assay demonstrated that ectopically expressed Olig2 repressed promoter activity of the gene encoding the major basic protein (MBP), while mutant Olig2 had no effect. Olig2 siRNA reversed the Olig2-mediated repressive effect on the MBP promoter activity. Whole-genome transcriptome and subsequent validation analyses using Olig2 siRNA-treated eosinophilic cells revealed that olig2 is involved in the biological processes for immune system and neurological system, and led to identification of a few downstream targets of Olig2, including CXCL10, Charcot-Leyden crystal protein, and IL6ST, all of which are implicated in immunomodulatory functions of eosinophils. Taken together, these results suggest Olig2 as a transcription factor that is expressed and regulate eosinophil immune functions in a stage- and lineage-specific manner, and also lead to proposition of Olig2 as a molecular target to intervene eosinophil-associated diseases.