Journal article
Effector Regulatory T Cell Differentiation and Immune Homeostasis Depend on the Transcription Factor Myb
S Dias, A D'Amico, E Cretney, Y Liao, J Tellier, C Bruggeman, FF Almeida, J Leahy, GT Belz, GK Smyth, W Shi, SL Nutt
Immunity | CELL PRESS | Published : 2017
Abstract
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 expre..
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Awarded by Australian National Health and Medical Research Council (NHMRC)
Funding Acknowledgements
We thank Jon Frampton (University of Birmingham) and Alexander Rudensky (Memorial Sloan Kettering Cancer Center) for mouse strains, John Stamatoyannopoulos and Richard Sandstrom (University of Washington) for assistance with the Treg cell DHS dataset, Jason Corby and Stephen Wilcox for technical assistance, Kylie Grieg for assistance in developing the Myb GFP strain, and Axel Kallies, Michael Chopin, Ajithkumar Vasanthakumar, and Daniel Gray for helpful comments on the manuscript. This project was supported by the Australian National Health and Medical Research Council (NHMRC) through program (1054618 to G.T.B. and S.L.N.) and project (1047313 to E.C. and 637325 to S.L.N.) grants and fellowships (to G.K.S. and S.L.N.). W.S. was supported by a Commonwealth Serum Laboratories Centenary Fellowship. This work was made possible through Victorian State Government Operational Infrastructure Support and the NHMRC Independent Research Institute Infrastructure Support Scheme (9000364).