Effector Regulatory T Cell Differentiation and Immune Homeostasis Depend on the Transcription Factor Myb

Publication date: 17 January 2017
Source:Immunity, Volume 46, Issue 1
Author(s): Sheila Dias, Angela D'Amico, Erika Cretney, Yang Liao, Julie Tellier, Christine Bruggeman, Francisca F. Almeida, Jamie Leahy, Gabrielle T. Belz, Gordon K. Smyth, Wei Shi, Stephen L. Nutt
FoxP3-expressing regulatory T (Treg) cells are essential for maintaining immune homeostasis. Activated Treg cells undergo further differentiation into an effector state that highly expresses genes critical for Treg cell function, although how this process is coordinated on a transcriptional level is poorly understood. Here, we demonstrate that mice lacking the transcription factor Myb in Treg cells succumbed 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 genomic footprint analyses revealed that Myb directly regulated a large proportion of the gene expression specific to effector Treg cells, identifying Myb as a critical component of the gene regulatory network controlling effector Treg cell differentiation and function.

Graphical abstract

Teaser

Treg cells can derive from either thymic or peripheral sources and can undergo further differentiation into an effector state in response to environmental cues. Dias and colleagues demonstrate that Myb is specifically required for the differentiation of thymus-derived effector Treg cells that play a non-redundant role in controlling immune homeostasis.


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