Abstract
It is currently unclear whether our classifications for T helper cell subtypes truly define stable lineages or rather they represent cells with a more flexible phenotype. This distinction is important for predicting the behavior of T helper cells during normal immune responses as well as in pathogenic conditions. Determining the mechanisms by which T helper cell lineage-defining transcription factors are expressed and subsequently regulate epigenetic and downstream gene regulatory events will provide insight into this complex question. Importantly, lineage-defining transcription factors that regulate epigenetic events have the potential to redefine the fate of the cell when they are expressed. In contrast, factors that regulate the events downstream of a permissive epigenetic environment will only have the capacity to modulate the underlying gene expression profile that is already established in that cell. Finally, mechanisms related to the antagonism versus cooperation between the lineage-defining factors for opposing T helper cell subsets will influence the characteristics of the cell. Here, we provide an overview of these topics by discussing epigenetic states in T helper cell subtypes as well as the mechanisms by which lineage-defining factors, such as T-bet, regulate gene expression profiles at both the epigenetic and general transcription level. We also examine some of what is known about the interplay between the T helper cell lineage-defining transcription factors T-bet, GATA3, Foxp3, RorĪ³t, and Bcl-6 and how this relates to the proper functioning of T helper cell subsets. Defining the mechanisms by which these factors regulate gene expression profiles will aid in our ability to predict the functional capabilities of T helper cell subsets.
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Abbreviations
- Bcl-6:
-
B cell lymphoma-6
- Foxp3:
-
Forkhead box P3
- H3K4:
-
Histone 3 Lysine 4
- H3K27:
-
Histone 3 Lysine 27
- HAT:
-
Histone acetyltransferase
- HDAC:
-
Histone deacetylase
- Jmjd3:
-
Jumonji C domain-containing protein 3
- RORĪ³t:
-
RAR-related orphan receptor gamma
- T-bet:
-
T-box expressed in T cells
- Tfh:
-
T follicular helper cell
- Th:
-
T helper
- Treg:
-
Regulatory T cell
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Acknowledgments
We thank members of the Weinmann lab for helpful discussions. The research performed in the authorsā lab is supported by grants from the NIAID (AI061061) and (AI07272-061A) and the American Cancer Society (RSG-09-045-01-DDC).
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Oestreich, K.J., Weinmann, A.S. (2011). Encoding Stability Versus Flexibility: Lessons Learned From Examining Epigenetics in T Helper Cell Differentiation. In: Murre, C. (eds) Epigenetic Regulation of Lymphocyte Development. Current Topics in Microbiology and Immunology, vol 356. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2011_141
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