Constitutive β-catenin signaling dysregulates DC differentiation resulting in inability to control microbial infection (INM2P.418)

摘要: The protozoan Toxoplasma gondii is the second most common cause of foodborne illness-related deaths in US and can be fatal to infants immunocompromised patients. Dendritic cells (DC) are required for immunity T. gondii, recently, DC Wnt/β-catenin signaling has been suggested control tolerance intestine. However, role this axis peripheral development function unknown. Using transgenic mice expressing DC-specific constitutively active β-catenin (DCEx3-/-), we surprisingly found that splenic CD8α developmentally related CD103 compartment were significantly expanded relative corresponding populations wild-type (WT) animals. Splenic a source IL-12, infection DCEx3-/- with resulted rapid lethality associated proinflammatory cytokine overproduction. Transcription factor Irf8 drives differentiation, flow cytometric analysis revealed strong upregulation upon stabilization. Confirming this, WT CD8α+Irf8+ displayed higher levels CD8- DC. Together, our data show targets during development, resulting expansion spleen periphery. This first study implicate subset differentiation provides novel insight into complex transcriptional network development.