Abstract
Aberrant microglia activity is associated with many neurological and psychiatric disorders, yet our knowledge about the pathological mechanisms is incomplete. Here, we describe a genetically defined microglia sublineage in mice which has the ability to suppress obsessive compulsion and anxiety symptoms. These microglia derive from precursors expressing the transcription factor Hoxb8. Selective ablation of Hoxb8-lineage microglia or the Hoxb8 gene revealed that dysfunction in this cell type causes severe over-grooming and anxiety-like behavior and stress responses. Moreover, we show that the severity of the pathology is set by female sex hormones. Together, our findings reveal that different microglia lineages have distinct functions. In addition, our data suggest a mechanistic link between biological sex and genetics, two major risk factors for developing anxiety and related disorders in humans.