Mouse pre-immunocytes as non-proliferating multipotent precursors of macrophages, interferon-producing cells, CD8α+ and CD8α– dendritic cells

Abstract

Abstract In this study we characterize in mouse bone marrow and peripheral blood a homogeneous cell subset expressing Ly6C, CD31 and CD11c, that can give rise to multiple cell types involved in the immune response. Under the aegis of M-CSF or GM-CSF these cells rapidly differentiate without division to either macrophages or immature dendritic cells, which can be further induced to mature by LPS stimulation. In fetal thymic organ cultures the same cells generate both CD8α+ and CD8α? dendritic cells in comparable proportion as found in normal thymus. The Ly6C+, CD31+ and CD11c+ cells express not only TLR2 and TLR4, which are characteristic of myeloid dendritic cells, but also TLR7 and TLR9, which conversely are characteristic of humaninterferon-producing cells. Moreover, following stimulation with influenza virus, they rapidly express high levels of IFN-α mRNA. Finally these precursors are increased in bone marrow and peripheral blood during systemic inflammation. These cells are defined as 'pre-immunocytes' to underline the fact that they serve in a flexible fashion multiple, and often divergent, functions required for theimmune response to pathogens.