Transcription factor Etv3 controls the tolerogenic function of dendritic cells (RNA-seq of Etv3 KO Tregs)

Dendritic cells (DC) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DC including tissue-derived migratory DC (migDC), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25low regulatory T cells (Treg), spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)-like disease, supporting the reported genetic association of human ETV3 with SLE. Etv3-deficient migDC upregulated multiple costimulatory molecules including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the Treg abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DC, and implicate it in the regulation of human autoimmunity. Overall design: RNA-seq was performed on regulatory T cells purified from the spleens of control and ETV3-deficient mice (3 replicates per genotype).