360 CBFβ2 is required for LC hemostasis and repopulation but not required for its embryonic development
Yu Q, Zhou L, and Mi Q. 360 CBFβ2 is required for LC hemostasis and repopulation but not required for its embryonic development. Journal of Investigative Dermatology 2020; 140(7):S45.
Journal of Investigative Dermatology
Langerhans cells (LCs), established through the differentiation of embryonic LC precursors, are the sole dendritic cell subpopulation in the epidermis and potent regulators of immune surveillance and tolerance. Unlike conventional DCs, LCs follow unique patterns of development and maintenance under steady and inflamed states. Several transcription factors are essential for LC differentiation, including Runx3, which functions by forming heterodimers with the non-DNA binding β-subunit, CBFβ (Core-Binding Factor Subunit Beta) 1 or 2. However, the roles of CBFβ in LC ontogeny, maintenance after birth and LCs repopulation remain unknown. To address if CBFβ2 is required for LC development, we generated Csf1rCreCBFb2fl/fl conditional knockout (Csf1r.CBFb2-KO) mice in which CBFβ2 was deficient in macrophage/monocytes and LC precursors from embryonic stage. We found that the specific deletion of CBFβ in CSF1R expressing cells resulted in a significant decrease in the number of LCs in adult mice compared to WT littermates, while there was no significant difference on LC precursors at embryonic E17.5 and P0 between the CBFβKO and WT mice. Furthermore, the conditional deletion of CBFβ2 dramatically blocked BM-derived MHCII+ Langerin+ long-term LC repopulation after exposing to UVC treatment. Thus, our data highly suggest that CBFβ is required for LCs self-renewing at steady state and controls LC repopulation at inflammatory state, but not required for its embryonic development.