Effector regulatory T cell differentiation and immune homeostasis depend on the transcription factor Myb. Mus musculus

FoxP3-expressing regulatory T (Treg) cells are essential to maintain immune homeostasis. Activated Treg cells undergo further differentiation into an effector state that highly express genes critical for Treg cell function. Here we demonstrate that mice lacking the transcription factor Myb in Treg cells succumb to a multi-organ inflammatory disease. Myb was specifically expressed in, and required for the differentiation of, thymus-derived effector Treg cells. The combination of transcriptome and DNA binding analyses revealed that Myb directly regulates a large proportion of the effector Treg cell specific gene expression in mouse and human cells. This study identifies a critical role for Myb in the gene regulatory network controlling effector Treg cell differentiation and function. Overall design: Transcriptional profiling of naïve, activated and effector Treg cell populations using RNA sequencing