Elf3 plays a role in regulating dendritic cell maturation and function (100.42)

Abstract

Abstract Elf3 belongs to the family of epithelium-specific Ets transcription factors and can be upregulated in non-epithelial cells upon cytokine stimulation. Among Ets family transcription factors, Elf3 is most highly induced during inflammation, yet its function is not well understood. Here we demonstrate an important role of Elf3 in regulating dendritic cell (DC) function. Intraperitoneal injection of ovalbumin (OVA)-Alum to Elf3-/- mice resulted in increased migration of DCs to the peritoneal space along with hypermaturation followed by increase in subsequent migration of DCs to the draining lymph nodes. In vitro cultured Elf3-/- DCs underwent spontaneous maturation in absence of any inflammatory stimuli and upon exposure to inflammatory stimuli underwent hypermaturation compared to Elf3+/+ DCs, indicating a role of Elf3 in regulation DC maturation. Elf3-/- mice had normal T cell development but mounted an exaggerated Th2 response upon OVA exposure. Naïve T cells cultured with Elf3-/- DCs showed impairment in Th1 and Th17 differentiation with an increased propensity for Th2 differentiation. This was mediated by an impairment of IL-6 and IL-12 production by Elf3-/- DCs. The impairment of IL-6 and IL-12 production was due to impairment of IL-6 and IL-12p40 gene induction in Elf3-/- DCs in response to inflammatory stimuli. Impairment of Th1 differentiation promoted Th2 differentiation. Taken together, our findings identify a role of Elf3 in regulating DC maturation and function.