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Master regulators or lineage-specifying? Changing views on CD4+ T cell transcription factors

Abstract

There is an emerging body of research demonstrating that the co-expression of key lineage-specifying transcription factors, commonly referred to as 'master regulators', affects the functional capabilities and flexibility of CD4+ T cell subsets. Here, we discuss how the natural co-expression of these lineage-specifying transcription factors has challenged the concept that the expression of a single 'master regulator' strictly establishes an absolute CD4+ T cell phenotype. Instead, it is becoming clear that the interplay between the lineage-specifying (or lineage-defining) transcription factors, including T-bet, GATA3, RORγt, BCL-6 and FOXP3, contributes to the fate and flexibility of CD4+ T cell subtypes. This in turn has led to the realization that CD4+ T cell phenotypes are more diverse than previously recognized.

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Figure 1: Co-expression of lineage-specifying transcription factors tips the balance in CD4+ T cell gene programmes.
Figure 2: T-bet–BCL-6 complexes prevent BCL-6 from binding to its target genes.

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Acknowledgements

We thank members of the Weinmann laboratory for lively discussions on this topic. The research in the authors' laboratory is supported by grants from the US National Institute of Allergy and Infectious Diseases (AI061061 and AI07272) and the American Cancer Society (RSG-09-045-01-DDC) to A.S.W.

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Correspondence to Amy S. Weinmann.

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Oestreich, K., Weinmann, A. Master regulators or lineage-specifying? Changing views on CD4+ T cell transcription factors. Nat Rev Immunol 12, 799–804 (2012). https://doi.org/10.1038/nri3321

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