The regulation of CD5 expression in murine T cells

Tung, James W.; Kunnavatana, Shaun S.; Herzenberg, Leonard A.; Herzenberg, Leonore A.

doi:10.1186/1471-2199-2-5

Cited by 21 publications

(4 citation statements)

References 48 publications

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“…In contrast, HVEM engagement increased phosphorylation of mitogen-activated protein kinase (MAPK) kinase (MEK) (Figure 4E). MEK activation can increase expression of E26 avian leukemia oncogene 1 (ETS1) as well as decrease an expression of transcription factor 3 (TCF-3 also known as E2A or E47), correspondingly, positive and negative regulators of Cd5 expression (Khanna et al, 2011; Page et al, 2004; Paumelle et al, 2002; Tung et al, 2001; Yang et al, 2004). We found a decreased expression of E2A (E47) and an increased expression and abundance of ETS1 in developing CD5 hi T cells, consistent with their specific functions in transcriptional regulation of Cd5 expression (Figure 4F–H).…”

Section: Resultsmentioning

confidence: 99%

Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells

et al. 2016

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Dendritic cells (DCs) initiate immunity and also antigen-specific tolerance mediated by extrathymic regulatory T (Treg) cells. Yet it remains unclear how DCs regulate induction of such tolerance. Here we report that efficient induction of Treg cells was instructed by BTLA+DEC205+CD8+CD11c+ DCs and the immunomodulatory functions of BTLA. In contrast, T cell activation in steady state by total CD11c+ DCs that include a majority of DCs that do not express BTLA did not induce Treg cells and had no lasting impact on subsequent immune responses. Engagement of HVEM, a receptor of BTLA, promoted Foxp3 expression in T cells through upregulation of CD5. In contrast, T cells activated in the absence of BTLA and HVEM-mediated functions remained CD5lo and therefore failed to resist the inhibition of Foxp3 expression in response to effector cell-differentiating cytokines. Thus DCs require BTLA and CD5-dependent mechanisms to actively adjust tolerizing T cell responses under steady state conditions.

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Section: Resultsmentioning

confidence: 99%

Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells

et al. 2016

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“…Potential targets of Ets1, including CD5 or TCR genes, have been identified in vitro ( Ho et al, 1990 ; Prosser et al, 1992 ; Tung et al, 2001 ; Arman et al, 2004 ) and in a large-scale ChIP study of Ets1 binding in the Jurkat human T cell line ( Hollenhorst et al, 2007 ). However, only a few genes, including IFN-γ ( Grenningloh et al, 2005 ) and Runx3 (this study) have been shown to both recruit and require Ets1 for their expression in vivo.…”

Section: Discussionmentioning

confidence: 99%

The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus

Zamisch

Tian

Grenningloh

et al. 2009

Journal of Experimental Medicine

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The transcription factor Ets1 contributes to the differentiation of CD8 lineage cells in the thymus, but how it does so is not understood. In this study, we demonstrate that Ets1 is required for the proper termination of CD4 expression during the differentiation of major histocompatability class 1 (MHC I)–restricted thymocytes, but not for other events associated with their positive selection, including the initiation of cytotoxic gene expression, corticomedullary migration, or thymus exit. We further show that Ets1 promotes expression of Runx3, a transcription factor important for CD8 T cell differentiation and the cessation of Cd4 gene expression. Enforced Runx3 expression in Ets1-deficient MHC I–restricted thymocytes largely rescued their impaired Cd4 silencing, indicating that Ets1 is not required for Runx3 function. Finally, we document that Ets1 binds at least two evolutionarily conserved regions within the Runx3 gene in vivo, supporting the possibility that Ets1 directly contributes to Runx3 transcription. These findings identify Ets1 as a key player during CD8 lineage differentiation and indicate that it acts, at least in part, by promoting Runx3 expression.

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“…Because of its tissuerestricted distribution (21), Elf-1 is a likely partner in the concerted regulation of the mCD3␦ gene. Moreover, Elf-1 has been shown to play a critical role in regulation of other T cell-specific genes, including CD3, CD4, and CD5 (22)(23)(24)(25). Studies with Ets-1-deficient mice showed defects in mature T cells but no defect in T cell development.…”

Section: Discussionmentioning

confidence: 99%

T Cell-specific Expression of the MurineCD3δ Promoter

Ji¹,

Gupta²,

Okamoto³

et al. 2002

Journal of Biological Chemistry

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T cell-specific expression of human and mouse CD3␦ is known to be governed by an enhancer element immediately downstream from the gene. Here we demonstrate by transgenic and in vitro studies that the murine CD3␦ (mCD3␦) promoter prefers to be expressed in cells of the T lineage. Deletion analyses of a promoter segment (؊401/؉48 bp) followed by transient transfections indicate that upstream elements between ؊149 and ؊112 bp contribute to full expression of the gene. Furthermore, a core promoter region ؊37/؉29 appears to contribute to a T cell specificity. Using substitution mutant scanning, four positive and one negative regulatory elements were found within the mCD3␦ core promoter. The first two positive elements comprise two classical initiator-like sites, which recruit TFII-I, whereas a third contains a functional Ets binding site. Immediately adjacent to the observed transcription start site is a negative element that utilizes the transcription regulator YY1. The last positive regulatory element contains a potentially functional CREB binding site and the minor transcriptional start site. Because NERF-2, Elf-1, and Ets-1 are expressed preferentially in lymphocytes and because, in addition, YY1 represses the promoter activity strongly in non-T cells, we conclude that the combination of these transcription factors contributes to the T cell-specific expression pattern of mouse CD3␦.Recent studies have shown that B and T lymphocytes and natural killer cells originate from a common stem progenitor (1, 2). One of the earliest events in commitment to development of the T cell lineage is expression of the CD3 genes, which even precedes TCR 1 -␤ rearrangement (3). Functionally the CD3␥, ␦, and ⑀ proteins form the scaffold upon which the TCR⅐CD3 complex or the pre-TCR⅐CD3 complex is assembled. The genes encoding the CD3␥, ␦, and ⑀ membrane proteins are tightly linked on chromosome 9 in the mouse and on chromosome 11 in human (4). The CD3␥ and ␦ promoters are oriented head to head as a divergently transcribed gene pair, their transcription start sites being around 1.5 kb apart (4). Remarkably, no regulatory principles that govern all three CD3 genes have been recognized so far. This is particularly striking because CD3␥ and CD3␦ appear to have evolved from one common ancestor gene relatively recently (5).Both the mouse and human CD3␦ gene comprise five exons that are organized in a similar fashion. A T cell-specific enhancer element ␦A is found immediately downstream from the 3Ј-untranslated region of mouse and human CD3␦ and is thought to govern the T cell-specific expression of the gene (3). A second element ␦B, which is found in the mouse only, increases the activity of the ␦A enhancer but has no activity by itself (3).Different lines of evidence indicate that expression of most T cell-specific genes is regulated by assembly of promoter and enhancer elements resulting in large complexes that comprise multiple transcription factors (6). Little is known about the CD3␦ promoter and its importance for continued expression...

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The regulation of CD5 expression in murine T cells

Cited by 21 publications

References 48 publications

Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells

Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells

The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus

T Cell-specific Expression of the MurineCD3δ Promoter

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