The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells

Egawa, Takeshi; Tillman, Robert E.; Naoe, Yoshinori; Taniuchi, Ichiro; Littman, Dan R.

doi:10.1084/jem.20070133071408c

Cited by 110 publications

(71 citation statements)

References 40 publications

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“…29,30 Several studies have revealed that Runx3 is required for the expression of CD8 in mature CD8 1 T cells by silencing CD4 expression because mice with conditional knockout of Runx3 have a significant reduction in CD8 1 cells. 31,32 Furthermore, Runx3 functions to skew naive CD4 1 T cells toward the Th1 lineage, and Runx3 and T-bet interact to enhance the expression of IFN-c and silence IL-4 in Th1-type cells. 33 Moreover, Runx1 and Runx3 are both involved in IL-17 production by T regulatory cells.…”

Section: Introductionmentioning

confidence: 99%

Runt-related transcription factor 3 is involved in the altered phenotype and function in ThPok-deficient invariant natural killer T cells

et al. 2014

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The interplay between the CD4-lineage transcription factor ThPok and the CD8-lineage transcription factor, runt-related transcription factor 3 (Runx3), in T-cell development has been extensively documented. However, little is known about the roles of these transcription factors in invariant natural killer T (iNKT) cell development. CD1d-restricted iNKT cells are committed to the CD4 1 CD8 2 and CD4 2 CD8 2 sublineages, which respond to antigen stimulation with rapid and potent release of T helper (Th) 1 and Th2 cytokines. However, previous reports have demonstrated a new population of CD8 1 NKT cells in ThPok-deficient mice. In the current study, we sought to determine whether Runx3 was involved in the re-expression of CD8 and function of iNKT cells in the absence of ThPok. We used mice lacking Runx3, ThPok or both and verified that Runx3 was partially responsible for the appearance of CD8 1 iNKT cells in ThPok knockout mice. Additionally, Runx3 participated in the immune response mediated by iNKT cells in a model of a-galactosylceramide-induced acute hepatitis. These results indicate that Runx3 is crucial for the phenotypic and functional changes observed in ThPok-deficient iNKT cells. and the canonical T-cell receptor a (TCRa) chain (Va14-Ja18 in mice and V24-J18 in humans) coupled to specific Vb chains (Vb8, Vb7 and Vb2 in mice and Vb11 in humans). These receptors are responsible for the interaction of NKT cells with CD1d molecules expressed on CD4 1 CD8 1 double-positive (DP) thymocytes. 1 NKT cells are classified into type I (defined as invariant (iNKT) or classical NKT cells) and type II based on the antigens recognized by each and their TCR repertoires. 2 Our study focused on type I NKT cells (hereafter referred to as iNKT cells). iNKT cells recognize the glycosphingolipid antigen a-galactosylceramide (a-GalCer) and a-GalCer loading with the tetrameric form of CD1d is often used to define the iNKT cell subset because of the high affinity of CD1d for the iNKT cell TCR. 3 Although iNKT cells originate from CD4 1 CD8 1 (DP) thymocytes 4 and are selected by MHC class

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Section: Introductionmentioning

confidence: 99%

Runt-related transcription factor 3 is involved in the altered phenotype and function in ThPok-deficient invariant natural killer T cells

et al. 2014

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“…Runx1 is also a good candidate gene whose decreased expression in the absence of c-Myb correlates with the impaired differentiation and proliferation in Myb-deficient thymocytes. Conditional deletion of Runx1 in DN2 thymocytes resulted in a partial block in DN3 to DN4 differentiation and impaired DN4 proliferation [284]. We also detect a partial block in DN3 to DN4 differentiation and impaired DN4 proliferation in Myb f/f C thymi.…”

Section: Itga9supporting

confidence: 49%

“…Expression of CD5 on DN thymocytes is dependent on pre-TCR and Lck activation [282], expression of CD2 is detected on TCRβ expressing DN thymocytes [283], and expression of CD27 is detected on large DN3 (DN3L) thymocytes that have initiated β-selection signaling. Whereas, a CD25 bright population of DN3 thymocytes [32] and CD25 expression on DP thymocytes [53,[284][285][286][287] Injection of Rag-1 or Rag-2-deficient mice with anti-CD3ε antibody is thought to mimic pre-TCR signaling and provides a sufficient signal to drive DN3 thymocytes to proliferate and differentiate to the DP stage [63]. We have previously reported that Myb f/f C DN3 thymocytes treated with anti-CD3ε differentiated to the DN4 stage [14].…”

Section: Thymocyte Specific Deletion Ofmentioning

confidence: 99%

“…Although we did not detect a difference in Pten, Bim or Glut1 expression according to our microarray analysis, it is possible that we are unable to detect cells with reduced expression of Pten, Bim or Glut1 because they quickly undergo apoptosis. In addition, conditional deletion of Runx1 in DN2 thymocytes resulted in a partial block in DN3 to DN4 differentiation and impaired DN4 proliferation [284]. A gene expression microarray performed on Runx1-null embryos suggested that Runx1 targets also include genes involved in cell motility, cell proliferation, and cytoskeletal organization according to a biological pathway analysis [313].…”

Section: Btg1mentioning

confidence: 99%

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MYB IS Required for B-Selection During Thymopoises

Duley¹

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Abstractc-Myb is a transcription factor required during hematopoiesis and is crucial for multiple stages of thymopoiesis. Understanding c-Myb function during hematopoiesis has been greatly impeded due to the lack of a tractable genetic system. We have used the Cre/loxP approach to conditional mutagenesis to study c-Myb function during thymopoiesis. Thymocyte specific inactivation of the Myb locus demonstrated a block in DN3 to DN4 differentiation concomitant with impaired Vβ to DJβ recombination of the Tcrb locus suggesting that the inability to generate a TCRβ protein blocked DN3 differentiation. However, some DN3 thymocytes

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“…It is thought that ThPOK functions as a commitment factor, antagonizing the CD8-specific transcriptional program (Egawa and Littman, 2008;Muroi et al, 2008;Wang et al, 2008a). One of the factors that ThPOK antagonizes is the runt domain transcription factor Runx3, which is critical for cytotoxic lineage development (Egawa et al, 2007;Taniuchi et al, 2002a). Runx3, analogous to ThPOK, is thought to act as a commitment factor that suppresses the helper transcriptional program (Egawa and Littman, 2008).…”

Section: Introductionmentioning

confidence: 99%

The Epigenetic Landscape of Lineage Choice: Lessons From the Heritability of Cd4 and Cd8 Expression

Gialitakis¹,

Sellars²,

Littman³

2011

Current Topics in Microbiology and Immunology

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Developing αβ T cells choose between the helper and cytotoxic lineages, depending upon the specificity of their T cell receptors for MHC molecules. The expression of the CD4 co-receptor on helper cells and the CD8 co-receptor on cytotoxic cells is intimately linked to this decision, and their regulation at the transcriptional level has been the subject of intense study to better understand lineage choice. Indeed, as the fate of developing T cells is decided, the expression status of these genes is accordingly locked. Genetic models have revealed important transcriptional elements and the ability to manipulate these elements in the framework of development has added a new perspective on the temporal nature of their function and the epigenetic maintenance of gene expression. We examine here the novel insights into epigenetic mechanisms that have arisen through the study of these genes.

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The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells

Cited by 110 publications

References 40 publications

Runt-related transcription factor 3 is involved in the altered phenotype and function in ThPok-deficient invariant natural killer T cells

Runt-related transcription factor 3 is involved in the altered phenotype and function in ThPok-deficient invariant natural killer T cells

MYB IS Required for B-Selection During Thymopoises

The Epigenetic Landscape of Lineage Choice: Lessons From the Heritability of Cd4 and Cd8 Expression

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