Cutting Edge: Histone Acetylation and Recombination at the TCRγ Locus Follows IL-7 Induction

Huang, Jiaqiang; Durum, Scott K.; Muegge, Kathrin

doi:10.4049/jimmunol.167.11.6073

Cited by 50 publications

(28 citation statements)

References 23 publications

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“…The first wave of hemopoietic precursors that migrates into the fetal thymus gives rise to thymocytes that express an invariant TCR␥␦ characterized by a lack of junctional diversity (51,52). IL-7R-mediated signals are required to initiate TCR␥ gene rearrangement (13)(14)(15). Therefore, it seems likely that the prevalence of IL-7-expressing TECs in the early fetal thymus is an important factor in establishing an appropriate intrathymic milieu for promoting ␥␦ T cell development.…”

Section: Discussionmentioning

confidence: 99%

“…IL-7 signaling also promotes the survival of DN thymocytes undergoing transition through the ␤-selection checkpoint to the CD4 ϩ CD8 ϩ double-positive (DP) stage (11) and proliferation of positively selected CD4 ϩ CD8 Ϫ and CD4 Ϫ CD8 ϩ singlepositive (SP) thymocytes (12). In addition to enhancing the survival and proliferation of ␣␤-lineage thymocytes, IL-7 regulates TCR␥ gene rearrangement by controlling locus accessibility, and is, therefore, essential for the development of ␥␦ T cells (13)(14)(15).…”

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confidence: 99%

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Ontogeny and Regulation of IL-7-Expressing Thymic Epithelial Cells

Zamisch

Moore-Scott²,

Su³

et al. 2005

The Journal of Immunology

117

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Epithelial cells in the thymus produce IL-7, an essential cytokine that promotes the survival, differentiation, and proliferation of thymocytes. We identified IL-7-expressing thymic epithelial cells (TECs) throughout ontogeny and in the adult mouse thymus by in situ hybridization analysis. IL-7 expression is initiated in the thymic fated domain of the early primordium by embryonic day 11.5 and is expressed in a Foxn1-independent pathway. Marked changes occur in the localization and regulation of IL-7-expressing TECs during development. IL-7-expressing TECs are present throughout the early thymic rudiment. In contrast, a major population of IL-7-expressing TECs is localized to the medulla in the adult thymus. Using mouse strains in which thymocyte development is arrested at various stages, we show that fetal and postnatal thymi differ in the frequency and localization of IL-7-expressing TECs. Whereas IL-7 expression is initiated independently of hemopoietic-derived signals during thymic organogenesis, thymocyte-derived signals play an essential role in regulating IL-7 expression in the adult TEC compartment. Moreover, different thymocyte subsets regulate the expression of IL-7 and keratin 5 in adult cortical epithelium, suggesting that despite phenotypic similarities, the cortical TEC compartments of wild-type and RAG-1−/− mice are developmentally and functionally distinct.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Ontogeny and Regulation of IL-7-Expressing Thymic Epithelial Cells

Zamisch

Moore-Scott²,

Su³

et al. 2005

The Journal of Immunology

117

View full text Add to dashboard Cite

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“…It appears as if the regulation of this rearrangement occurs through STAT5 histone acetylation (37,38).…”

Section: The Role Of Il-7 In the Development Of T-cellsmentioning

confidence: 99%

The role of IL-7 in Immunity and Cancer

2017

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Abstract. Interleukin-7 (IL-7) is a cytokine that has been known since long in immunology, mainly regarding its effects on T-cells and B-cells. IL-7 has been demonstrated to be necessary for both B-cell and T-cell proliferation and lack of IL-7 causes immature immune cell arrest. Interestingly, in recent years, certain studies have strongly suggested that the role of IL-7 is far beyond the field of immunology, it might have direct or indirect effect on cancer. This review aims to summarize the role of IL-7 in immunity and its role in the pathogenesis of neoplasia.

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“…Rearrangement-and transcription-permissive chromatin is usually associated with acetylated histones 3 or 4 (AcH3 or AcH4) 32 . It has been shown previously by semi-quantitative chromatin immunoprecipitation (ChIP) assays that the TcrC γ 1 locus in Il7r -/-thymocytes is relatively inaccessible 16,33 . This conclusion was based on the fact that the J γ gene segment, the 3′ enhancer (E Cγ1 ), as well as the locus control region-like element (DNaseI hypersensistive site A, HsA 14,34 ), of the TcrC γ 1 locus are hypoacetylated.…”

Section: Il-15 Modulates Chromatin Accessibility Of V γ 5 Genementioning

confidence: 99%

Interleukin 15 controls the generation of the restricted T cell receptor repertoire of γδ intestinal intraepithelial lymphocytes

2005

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AbstractγδT cells are prevalent in the mucosal epithelia and are postulated to act as sentries to maintain tissue integrity. What these γδT cells recognize is poorly defined, but based on the restricted T cell receptor (TCR) repertoire, the notion that they are selected by self-antigens of low complexity has been widely disseminated. We present data demonstrating that generation of the restricted TCR Vγ gene repertoire of intestinal intraepithelial lymphocytes is regulated by IL-15, which induces Vγ gene segmentspecific local chromatin modifications and enhanced accessibility conducive for subsequent targeted gene rearrangement. This cytokine-directed tissue-specific TCR repertoire formation likely reflects distinct TCR repertoire selection criteria for γδ and αβT cell lineages adopted for different antigen recognition strategies.Intestinal intraepithelial lymphocytes (i-IELs) found within the intestinal epithelial layer are an essential component of mucosal immunity. Similar to T cell subsets in other lymphoid tissues, i-IELs are composed of two T cell types, αβ and γδT cells. In contrast to other tissues, however, γδT cells are prevalent in the mucosal epithelia of most vertebrates and are thought to be a major source of secreted factors necessary for the maintenance of tissue integrity subsequent to infection, transformation, or cell injury 1-3 .Despite the long history of i-IELs, their origin and ligand specificity remain uncertain. Earlier work has indicated that αβ i-IELs originate exclusively from the thymus in normal mice 4 , but whether γδ i-IELs are subject to similar developmental constraints is unclear. The majority of human and mouse γδ i-IELs express the homodimeric αα form of the CD8 coreceptor and exhibit restricted Variable (V) γ and V δ gene usage. In C57BL/6 (B6) mice, for example, V γ 5 expressing cells constitute the predominant i-IEL population in the small intestine [5][6][7] . Mouse strain-specific preferential usage of Tcrg and Tcrd genes among i-IELs arises from complex molecular and cellular controls with evidence for genetic linkage to the Tcrg, Tcrd and H2 loci 6,8,9 , but the exact mechanism is unknown. Two non-mutually exclusive mechanistic processes can be considered to account for the restricted TCR gene usage: cellular selection and programmed TCR gene rearrangement. A hallmark of adaptive immunity is the cellular selection process geared toward forming a population of cells with antigen receptor repertoires that can recognize the entire external universe of antigens. This selection pressure acts on immature cell subsets expressing randomly generated clonal antigen receptors. Although the TCR-driven selection shaping the αβTCR repertoire of conventional αβT cells constitutes a fundamental theme in immunology, whether a similar process is needed for γδT cell development, and specifically for γδ i-IELs, remains a matter of debate [10][11][12] .

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Cutting Edge: Histone Acetylation and Recombination at the TCRγ Locus Follows IL-7 Induction

Cited by 50 publications

References 23 publications

Ontogeny and Regulation of IL-7-Expressing Thymic Epithelial Cells

Ontogeny and Regulation of IL-7-Expressing Thymic Epithelial Cells

The role of IL-7 in Immunity and Cancer

Interleukin 15 controls the generation of the restricted T cell receptor repertoire of γδ intestinal intraepithelial lymphocytes

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