The transcription factor Batf3 inhibits the differentiation of regulatory T cells in the periphery

Naive CD4 T cells activated by antigen-presenting cells (APCs) undergo terminal differentiation in the periphery. Multiple mechanisms determine their fates, that is, whether they differentiate into conventional T (Tconv) cells or regulatory T (Treg) cells. The key event during Treg generation is expression of the transcription factor Foxp3, which is the lineage-determining regulator for Treg differentiation and function. Here we show that the transcription factor Batf3 acts as a fate-decision factor with respect to Tconv versus Tregs by restraining Treg differentiation. Batf3 was preferentially expressed in effector CD4 T cells but not in Treg cells, and ectopic expression of Batf3 inhibited Foxp3 induction. Batf3-deficient CD4 T cells favorably differentiated into Treg cells in vitro and in colonic lamina propria. Batf3 KO mice also showed enhanced Treg function in gut-associated immune disease models (for example, ovalbumin tolerance and inflammatory bowel disease models). Batf3 bound to the CNS1 region of the Foxp3 locus and reduced expression of the gene. Thus, Batf3 is a transcriptional suppressor of Treg differentiation. Researchers have clarified the role of a protein that prevents T helper cells from developing into regulatory T cells. Treg cells stop other immune cells from attacking the body's own tissues. The transcription factor Foxp3, a protein controlling the rate of transcribing genetic information, is key to Treg cell generation. A team headed by Gap Ryol Lee at Seoul's Sogang University investigated Foxp3 expression in Treg cell development. The authors found that the transcription factor Batf3 was expressed in T helper cells, but not in Treg cells, and that expression of Batf3 inhibited Foxp3. They observed that T helper cells deficient in Batf3 could develop into Treg cells in cell culture and in animal experiments. The team determined that Batf3 bound to the Foxp3 gene and reduced its expression. Targeting the function of Batf3 may offer therapeutic possibilities.