Unique role of Cbfβ2 variant in Langerhans cell development (P4492)

Abstract

Abstract In mammals, Cbfβ protein, known as an essential subunit of Runx transcription factor complexes, are present as two RNA splicing variants, Cbfβ1 and Cbfβ2. To address in vivo roles of individual variant, we have generated mutant mouse strain lacking either Cbfβ1 or Cbfβ2. Here we show that a loss of Cbfβ2 variant results in a defect in Langerhans cell development. In the ear epidermis of adult Cbfβ2-deficient mice, no mature Langerhans cells expressing Langerin and EpCAM were detected. Instead, there were a few larger cells with characteristics of immature Langerhans precursors, such as the dendritic morphology and the expression of MHC class II and CX3CR1. Analysis of bone marrow chimera showed that these Langerin−EpCAM−classII+ cells were radio-resistant residential cells that could not be replaced by donor cells. Analyses of ontogeny of Langerhans cell development around neonatal stage revealed that seeding of CD45+ early progenitor cell to the skin occurred normally in Cbfβ2-deficient mice. However, the next transition into Langerin+EpCAM+ stage, which is know to require for TGFβ signals around day 3 after birth, was severely impaired in the absence of Cbfβ2. Interestingly, although immature Langerhans precursors disappear in adult epidermis by lack of TGFβR1 signals, our results indicate that those cells are stably maintained in the Cbfβ2-deficient mice, suggesting an unique role of Runx3/Cbfβ2 complexes in regulating Langerhans cell development.