Definition of a mouse microglial subset that regulates neuronal development and proinflammatory responses in the brain

Expression of Itgax (encoding the CD11c surface protein) and Spp1 (encoding osteopontin; OPN) has been associated with activated microglia that can develop in healthy brains and some neuroinflammatory disorders. However, whether CD11c and OPN expression is a consequence of microglial activation or represents a portion of the genetic program expressed by a stable microglial subset is unknown. Here, we show that OPN production in the brain is confined to a small CD11c+ microglial subset that differentiates from CD11c2 precursors in perinatal life after uptake of apoptotic neurons. Our analysis suggests that coexpression of OPN and CD11c marks a microglial subset that is expressed at birth and persists into late adult life, independent of environmental activation stimuli. Analysis of the contribution of OPN to the intrinsic functions of this CD11c+ microglial subset indicates that OPN is required for subset stability and the execution of phagocytic and proinflammatory responses, in part through OPN-dependent engagement of the alpha V beta 3-integrin receptor. Definition of OPN-producing CD11c+ microglia as a functional microglial subset provides insight into microglial differentiation in health and disease.