Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal γδ T cells

Boyden, Lynn M.; Lewis, Julia M.; Barbee, Susannah D.; Bas, Anna; Girardi, Michael; Hayday, Adrian; Tigelaar, Robert E.; Lifton, Richard P.

doi:10.1038/ng.108

Cited by 267 publications

(281 citation statements)

References 29 publications

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“…Moreover, Pro1 and Pro2 transcripts were not present in mature fetal thymic Vg3 T cells either (Fig. 4B), which are TCR triggered in vivo during positive selection (6,8). Collectively, these results reveal that TCR-mediated induction of Ly49E expression on intraepithelial gd T cells and their precursors is regulated by a promoter different from Pro1 and Pro2.…”

Section: De Novomentioning

confidence: 80%

“…As such, our data further confirm that thymic differentiation from immature CD24 high CD122 2 Ly49E 2 into mature CD24 low CD122 + Ly49E low Vg3 T cells is driven by TCR-mediated cell activation or positive selection. This was elegantly shown by the laboratory of A. Hayday by investigation of FVB-Tac mice, in which Vg3 T cells maintain an immature phenotype due to Skint-1 deficiency, which can be complemented by engaging thymocytes with agonist anti-TCR Abs (7,8).…”

Section: Discussionmentioning

confidence: 94%

“…These gd + intraepithelial lymphocytes generally display a restricted TCR repertoire (1) and are potent cytolytic and immunoregulatory effectors that protect host tissues from infection, cell transformation, and uncontrolled infiltration by circulating cells (2,3). Among them, Vg3 T cells [nomenclature by Garman et al (4)] are the first T cells to arise in the fetal thymus (5), where they differentiate from immature CD24 high CD122 2 into mature CD24 low CD122 + cells upon skint1-mediated positive selection (6)(7)(8). Positively selected Vg3 T cells home to the epidermis before birth, where they are called dendritic epidermal T cells (DETCs) and where they sustain the population for the life of the animal (5).…”

mentioning

confidence: 99%

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DifferentialLy49eExpression Pathways in Resting versus TCR-Activated Intraepithelial γδ T Cells

Broeck

Ammel

Delforche

et al. 2013

The Journal of Immunology

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The Ly49 NK receptor family in mice is composed of several members that recognize MHC class I (MHC-I) or MHC-I–related molecules. We and others have shown before that Ly49E is a unique member, with a different expression pattern on NK cells and being triggered by the non–MHC-I–related protein urokinase plasminogen activator. Among the entire Ly49 receptor family, Ly49E is the only Ly49 member expressed by epidermal-localized γδ T cells and their fetal thymic TCRγδ precursors, and it is the most abundantly expressed member on intestinal intraepithelial γδ T cell lymphocytes. In this study, we provide mechanistic insights into the regulation of Ly49e expression in γδ T cells. First, we demonstrate that TCR-mediated activation of intraepithelial γδ T cells significantly increases Ly49E expression. This results from de novo Ly49E expression and is highly selective, because no other Ly49 family members are induced. TCR-mediated Ly49E induction is a conserved feature of skin- and gut-residing intraepithelial-localized γδ T cell subsets, whereas it is not observed in spleen γδ T cells. By investigating Ly49e promoter activities and lymphotoxin (LT) αβ dependency in resting versus TCR-activated intraepithelial γδ T cells, we reveal two separate regulatory pathways for Ly49E expression, as follows: a LTαβ-dependent pathway leading to basal Ly49E expression in resting cells that is induced by Pro2-mediated Ly49e transcription, and a LTαβ-independent pathway leading to elevated, Pro3-driven Ly49E expression in TCR-stimulated cells.

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Section: De Novomentioning

confidence: 80%

Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

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DifferentialLy49eExpression Pathways in Resting versus TCR-Activated Intraepithelial γδ T Cells

Broeck

Ammel

Delforche

et al. 2013

The Journal of Immunology

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“…Similarly, no inherent MHC bias seems to exist with the BCRs. However, it remains possible that cd TCRs have inherent biases for the recognition of cell surface molecules other than MHC, 23 and given the limitation of the repertoire outside of CDR3d, this even seems likely. 24 No such bias or restricting element has been firmly established, however.…”

Section: Mechanism Of Ligand Recognitionmentioning

confidence: 99%

Diversity of γδ T-cell antigens

2012

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In the last two decades, it has become clear that cd T cells recognize a diverse array of antigens including self and foreign, large and small, and peptidic and non-peptidic molecules. In this respect, cd antigens as a whole resemble more the antigens recognized by antibodies than those recognized by ab T cells. Because of this antigenic diversity, no single mechanism-such as the major histocompatibility complex (MHC) restriction of ab T cells-is likely to provide a basis for all observed T-cell antigen receptor (TCR)-dependent cd T-cell responses. Furthermore, available evidence suggests that many individual cd T cells are poly-specific, probably using different modes of ligand recognition in their responses to unrelated antigens. While posing a unique challenge in the maintenance of self-tolerance, this broad reactivity pattern might enable multiple overlapping uses of cd T-cell populations, and thus generate a more efficient immune response.

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“…SOX13, 1 Id3, 2 T-cell receptor (TCR) signal strength, etc. [3][4][5][6][7][8][9][10] However, mechanisms of functional differentiation of effector cd T cells are poorly understood. [11][12][13][14] Key cytokines produced by cd T cells are interferon (IFN)-c, [15][16][17][18][19] tumor-necrosis factor (TNF)-a 20,21 and IL-17, [22][23][24][25][26] and are critical for pathogen clearance, immune regulation and autoimmunity.…”

Section: Developmentmentioning

confidence: 99%

Current progress in γδ T-cell biology

Hao

Xia

et al. 2010

Cell Mol Immunol

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T lymphocytes bearing c-and d-chain T-cell receptor heterodimers are named cd T cells. Interestingly, cd and ab T cells share the same progenitors, and they undergo a fate decision in the thymus. Functional differentiation of cd T cells occurs both inside and outside the thymus. Antigen recognition of cd T-cell receptors is very unique, and the responses frequently exhibit innate characteristics. Nevertheless, peripheral cd T cells exert a number of effector and regulatory functions. cd T cells rapidly produce cytokines like interferon (IFN)-c and IL-17 and promote inflammation, partly due to the inherent epigenetic and transcriptional programs, which facilitates a quick and extensive response. Moreover, cd T cells lyse target cells directly, and this is necessary for pathogen or tumor clearance. cd T cells can even serve as regulatory cells, and may contribute to immune suppression. Orchestration of cd T-cell and other immune cell interactions may be critical for host defense and immune regulation. Recently, cd T cells have been used for immunotherapy for infectious diseases and malignancy. In this review, we summarize the abstracts presented at the recent cd T cell Conference held from 19 to 21 May 2010, in Kiel, Germany (please see the website for details: http://www.gammadeltaconference.uni-kiel.de/index.html). Peptide-major histocompatibility complex-specific T-cell responses are known to be achieved by ab T cells, while cd T-cell biology is much less studied. Mice without cd T cells are highly susceptible to diseases and tumor, suggesting an important role of cd T cells in defense. By current technology in cellular and molecular immunology, researchers revealed that cd T cells produce a series of cytokines in pathology, and the effector cd T cells play an indispensable role in pathogen elimination, immune regulation and autoimmunity. As a group of innate immune cells, cd T cells respond rapidly and expand efficiently when stimulated by antigens or cytokines. cd T cells may be a good target for modulation of immune responses in human diseases. In recent years, a lot of researchers focused on the cd T-cell development, function and therapeutic use.

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Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal γδ T cells

Cited by 267 publications

References 29 publications

DifferentialLy49eExpression Pathways in Resting versus TCR-Activated Intraepithelial γδ T Cells

DifferentialLy49eExpression Pathways in Resting versus TCR-Activated Intraepithelial γδ T Cells

Diversity of γδ T-cell antigens

Current progress in γδ T-cell biology

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