HEB in the Spotlight: Transcriptional Regulation of T-Cell Specification, Commitment, and Developmental Plasticity

Braunstein, Marsela; Anderson, Michele K.

doi:10.1155/2012/678705

Cited by 34 publications

(34 citation statements)

References 124 publications

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“…HEBAlt appears to function redundantly with HEB, given that ectopic expression of HEBAlt in Heb-deficient cells restored the generation of DP progenitors (241). HEB proteins may also play a role in inhibiting myeloid and NK cell fates in T cell progenitors (242).…”

Section: Distinct Programs Of T Cells and Ilcsmentioning

confidence: 99%

Transcriptional Regulation of Innate and Adaptive Lymphocyte Lineages

Obaldia

Bhandoola

2015

Annu. Rev. Immunol.

153

128

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The lymphocyte family has expanded significantly in recent years to include not only the adaptive lymphocytes (T cells, B cells) and NK cells, but also several additional innate lymphoid cell (ILC) types. ILCs lack clonally distributed antigen receptors characteristic of adaptive lymphocytes and instead respond exclusively to signaling via germline-encoded receptors. ILCs resemble T cells more closely than any other leukocyte lineage at the transcriptome level and express many elements of the core T cell transcriptional program, including Notch, Gata3, Tcf7, and Bcl11b. We present our current understanding of the shared and distinct transcriptional regulatory mechanisms involved in the development of adaptive T lymphocytes and closely related ILCs. We discuss the possibility that a core set of transcriptional regulators common to ILCs and T cells establish enhancers that enable implementation of closely aligned effector pathways. Studies of the transcriptional regulation of lymphopoiesis will support the development of novel therapeutic approaches to correct early lymphoid developmental defects and aberrant lymphocyte function.

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Section: Distinct Programs Of T Cells and Ilcsmentioning

confidence: 99%

Transcriptional Regulation of Innate and Adaptive Lymphocyte Lineages

Obaldia

Bhandoola

2015

Annu. Rev. Immunol.

153

128

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“…In the absence of E2A, excess GATA3 causes a block in T cell development, whereas E2A 2/2 multipotent progenitors knocked down for Gata3 by small interfering RNA were able to generate DN3 cells (25). The role of E proteins, including E2A and E2-2, in thymocyte development is covered in a recent review (26). The relationship between Notch and Gata3 remains complex; however, both are clearly required for the development of ETPs and thymocytes.…”

Section: Tsp To Dn2 Stagesmentioning

confidence: 99%

“…HEB proteins are bHLH family transcription factors implicated in several stages of thymocyte differentiation: b-selection, TCRb and TCRa gene rearrangements, regulation of pre-TCRa, and CD4 expression (26,44). Separate transcriptional start sites in HEB give rise to canonical and shorter alternate (HEBAlt) forms (26).…”

Section: Dn2a/b To Dn3 Stagesmentioning

confidence: 99%

“…Separate transcriptional start sites in HEB give rise to canonical and shorter alternate (HEBAlt) forms (26). A developmental block in HEB 2/2 cells observed at the b-selection checkpoint can be partially restored with transgenic expression of HEBAlt, bypassing b-selection, to the DP stage, thus implicating HEBAlt as a critical regulator of early T-lineage genes (45).…”

Section: Dn2a/b To Dn3 Stagesmentioning

confidence: 99%

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An Overview of the Intrathymic Intricacies of T Cell Development

Shah

Zúñiga‐Pflücker

2014

The Journal of Immunology

198

157

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The generation of a functional and diverse repertoire of T cells occurs in the thymus from precursors arriving from the bone marrow. In this article, we introduce the various stages of mouse thymocyte development and highlight recent work using various in vivo, and, where appropriate, in vitro models of T cell development that led to discoveries in the regulation afforded by transcription factors and receptor–ligand signaling pathways in specifying, maintaining, and promoting the T cell lineage and the production of T cells. This review also discusses the role of the thymic microenvironment in providing a niche for the successful development of T cells. In particular, we focus on advances in Notch signaling and developments in Notch ligand interactions in this process.

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“…Stat3 promotes differentiation towards Th2 and Th17 profiles, 31 and GATA3 inhibits differentiation toward a Th1 profile and promotes differentiation toward a Th2 profile. [32][33][34] In summary, dietary YCA may promote T-cell differentiation toward a response that focuses on intracellular pathogens (Th1 response). Besides dehydrated S. cerevisiae, YCA contains fermentation product of the fungus T. longibrachiatum and may induce an immune response either directly or by altering the microbiota.…”

Section: Dietary Yca Increased Expression Of Genes Involved In T-cellmentioning

confidence: 99%

Yeast-containing feed additive alters gene expression profiles associated with innate immunity in whole blood of a rodent model

et al. 2016

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Feeding a yeast-containing additive (YCA; OmniGen-AF) improves immune responses in ruminant livestock and reduces subsequent production losses. The objective was to identify molecular pathways by which dietary YCA may modify immune responses using a rodent model. Thirty-seven healthy, unchallenged CD rats received a diet containing 0 (control; n = 5, only 28 d), 0.5% (n = 15) or 1% (n = 17) YCA for 7 (n = 4/group), 14 (n = 3 or 4/group), 21 (n = 3 or 4/group) or 28 (n = 5/group) d. At the end of the feeding periods, whole blood was collected and the isolated RNA was analyzed for the expression of 84 genes involved in innate and cell-mediated adaptive immune responses. Three bacterial pattern recognition receptors TLR1 (0.5%: + 2.01; 1%: + 2.38), TLR6 (0.5%: + 2.11; 1%: + 2.34) and NOD2 (0.5%: + 2.32; 1%: + 2.23), two APC surface receptors CD1D1 (0.5%: + 1.75; 1%: + 2.33) and CD80 (0.5%: +2.45; 1%: +3.00), and the cell signaling molecule MAPK8 (0.5%: +1.87; 1%: +2.35) were significantly up-regulated by YCA at both inclusion rates. In conclusion, feeding YCA may potentially increase recognition and responses to bacterial pathogens and T-cell activation and differentiation and thereby maintain health and prevent production losses.

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HEB in the Spotlight: Transcriptional Regulation of T-Cell Specification, Commitment, and Developmental Plasticity

Cited by 34 publications

References 124 publications

Transcriptional Regulation of Innate and Adaptive Lymphocyte Lineages

Transcriptional Regulation of Innate and Adaptive Lymphocyte Lineages

An Overview of the Intrathymic Intricacies of T Cell Development

Yeast-containing feed additive alters gene expression profiles associated with innate immunity in whole blood of a rodent model

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