T helper cells tailor the immune response by differentiating into one of a number of effector lineages. It has become apparent that these lineages are plastic and cells can switch phenotype. We have recently discovered that the Th1 lineage-specifying transcription factor T-bet can redistribute the Th2 regulator Gata3 away from its normal binding sites at Th2 genes. We hypothesise that this mechanism allows lineage-specification to proceed whilst maintaining a degree of developmental plasticity. This project aims to identify the mechanism through which T-bet controls Gata3 gene targeting and the importance of this for T cell lineage specification and plasticity.
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Evans C.M. and Jenner R.G. (2013). Transcription factor interplay in T helper cell differentiation. Brief Funct Genomics. 12(6): 499–511.
Kanhere A., Hertweck A., Bhatia U., Gokmen R., Perucha, E., Jackson I., Lord G.M., and Jenner R.G. (2012). T-bet and GATA3 orchestrate Th1 and Th2 cell differentiation through lineage-specific targeting of distal regulatory elements. Nat. Commun. 3:1268.
Jenner R.G., Townsend M.J., Sun K., Jackson I., Bouwman R.D., Young R.A., Glimcher L.H. and Lord G.M. (2009). The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes. Proc. Natl. Acad. Sci. USA. 106:17876-1788
Powell N., Walker A.W., Stolarczyk E., Canavan J.B., Gökmen M.R., Marks E., Jackson I., Hashim A., Curtis M.A., Jenner R.G., Howard J.K., Parkhill J., Macdonald T.T., Lord G.M. (2012). The Transcription Factor T-bet Regulates Intestinal Inflammation Mediated by Interleukin-7 Receptor(+) Innate Lymphoid Cells. Immunity 37:674-84.