Elf3 regulates dendritic cell driven T cell differentiation (99.1)

Abstract Elf3 belongs to the family of epithelium specific Ets transcription factors and can be upregulated in non-epithelial cells upon cytokine stimulation. Elf3-/- mice have normal T cell development and T cell differentiation into different T helper lineages. Here we show that upon epicutaneous sensitization with ovalbumin(OVA) followed by OVA intranasal challenge, Elf3-/- mice display a defect in Th17 induction, though OVA specific IgE and IgG1 antibody titers are several folds higher and airway inflammation is more extensive compared to Elf3+/+ mice, indicating an exaggerated Th2 response. Furthermore, intraperitoneal sensitization of Elf3-/- mice with OVA followed by OVA intranasal challenge, confirmed that Elf3-/- mice mounted an exaggerated Th2 response. Since, dendritic cells (DCs) are key players in initiation of adaptive immune response, we analyzed DC migration upon OVA challenge and showed that pulmonary DCs underwent hyperactivation in Elf3-/- mice compared to Elf3+/+ mice and rates of DC migration to the airway draining lymph nodes were also significantly higher in Elf3-/- mice, indicating that DCs may mediate the exaggerated Th2 response observed in Elf3-/- mice. Further analysis revealed that Elf3-/- DCs are more prone to maturation than Elf3+/+ DCs and upon maturation, Elf3-/- DCs preferentially secrete chemokines/cytokines that are important in polarizing Th2 differentiation. Taken together, these findings reveal a role of Elf3 in DC driven T cell differentiation.