Estrogen receptors promote langerin+ dendritic cell differentiation and migration from skin during inflammation in vivo (91.3)

CD207/langerin+ dendritic cells in the epidermis (eLC) and dermis (dLC) initiate immune responses in the skin. We previously published that estrogen receptor alpha (ERα) signaling promotes the differentiation of langerin+ DC in a GM-CSF-driven culture model. To compare the efficiency of dLC differentiation from ERα+ and ERα-/- bone marrow (BM) cells in vivo, we generated mixed competitive ERα+/ERα-/- BM chimeric mice. In the radiation-induced inflammatory environment early after reconstitution, dLC in cutaneous lymph nodes (cLN) were derived preferentially from ERα+ BM cells, indicating that during systemic inflammation ERα signaling promotes dLC differentiation from short term repopulating progenitors. To determine the relative ability of ERα+ and ERα-/- LC to become activated during local skin inflammation, green fluorescent dye in acetone/dibutylphthalate was applied to the skin of ERα+ and ERα-/- mice. Compared to ERα-/- mice, after 24 hr, ERα+ mice contained significantly greater numbers of langerin+ CD11b+ eLC that had acquired the green dye and migrated to cLN. Moreover, ERα+ mice contained higher numbers of new inflammatory CD11bhi CD11clo F4/80+ myeloid cells in the spleen. In sum, ERα signaling in response to endogenous estrogens promotes the development, activation and migration of skin-derived langerin+ DC during inflammation in vivo. Supported by OCAST HR06-157 & NIH AI079616, RR020143RR020143.