The V–J Recombination of  T Cell Receptor-γ Genes Is Blocked in Interleukin-7 Receptor–deficient Mice

Maki, Kazushige; Sunaga, Shinji; Ikuta, Koichi

doi:10.1084/jem.184.6.2423

Cited by 124 publications

(89 citation statements)

References 35 publications

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“…Furthermore, IL-7 participates in regulation of the maintenance and the strength of the immune response and regulates the development and the cytolytic activity of intestinal ␥␦ intraepithelial lymphocytes (36,40,41). These intraepithelial lymphocytes represent the frontline defense alimentary and bacterial gut lumen Ags and depend on IL-7R␣ signaling (42). Thus, IL-7R␣ signals IL-7-mediated critical specific actions on T cell development and function, yet the control of its expression remains obscure.…”

Section: Discussionmentioning

confidence: 99%

Positive Effects of Glucocorticoids on T Cell Function by Up-Regulation of IL-7 Receptor α

Franchimont

Galon

Vacchio

et al. 2002

The Journal of Immunology

145

102

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Despite the effects of glucocorticoids on immune function, relatively little is known about glucocorticoid-inducible genes and how their products may regulate lymphocyte function. Using DNA microarray technology to analyze gene expression in PBMC from healthy donors, we identified IL-7Rα as a glucocorticoid-inducible gene. This observation was confirmed at the mRNA and protein levels. Conversely, TCR signaling decreased IL-7Rα expression, and the relative strength of signaling between these two receptors determined the final IL-7Rα levels. The up-regulation of IL-7Rα by glucocorticoids was associated with enhanced IL-7-mediated signaling and function. Moreover, IL-7-mediated inhibition of apoptosis at increasing concentrations of glucocorticoids is consistent with enhanced cell sensitivity to IL-7 following glucocorticoid exposure. These observations provide a mechanism by which glucocorticoids may have a positive influence on T cell survival and function.

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Section: Discussionmentioning

confidence: 99%

Positive Effects of Glucocorticoids on T Cell Function by Up-Regulation of IL-7 Receptor α

Franchimont

Galon

Vacchio

et al. 2002

The Journal of Immunology

145

102

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“…Crompton et al found that the introduction of a transgenic TCR in IL-7 receptor ␣-deficient animals reconstituted thymocyte development, suggesting that the failure to undergo TCR ␣␤ gene rearrangements is one cause of the developmental block in the absence of IL-7R signaling [43]. In addition, IL-7 has been shown to be required for V-J recombination of TCR ␥ chain genes [44]. This latter finding provides an explanation for the complete absence of ␥␦ T cells in IL-7-, Jak3-, and ␥c-deficient mice.…”

Section: Early T Cell Maturation In the Thymus Of Adult Jak3-deficienmentioning

confidence: 99%

T cell development and activation in Jak3-deficient mice

Baird

Thomis

Berg

1998

Journal of Leukocyte Biology

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Jak3, a member of the Janus family of tyrosine kinases, participates in signaling through cytokine receptors that contain the common ␥-chain, including the receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15. Jak3-and ␥c-deficient mice have pleiotropic defects that can be attributed to their inability to respond to multiple specific cytokines. A great deal of recent work has focused on the T cell defects in these mutant mice. Specifically, Jak3-and ␥c-deficient mice have small thymuses revealing a defect in T cell development, and in addition, have functionally unresponsive peripheral T cells with an activated/memory cell phenotype. The thymic defect in these mutant mice strongly resembles that seen in IL-7 and IL-7 receptor knockout mice, suggesting that the lack of IL-7 receptor signaling accounts for this defect in Jak3 -/-and ␥c ؊ mice. To characterize this defect further, we have examined the earliest stages of T cell development in adult and fetal Jak3 -/-thymuses. These studies identify two discrete developmental defects at the CD4 ؊ CD8 ؊ stage of T cell maturation. Analyses of peripheral T cells in Jak3 -/-and ␥c ؊ mice have also revealed a number of abnormalities. All of the T cells in these mutant mice have an activated phenotype and a large fraction of them are proliferating in vivo. In addition, Jak3 -/-and ␥c ؊ T cells are more prone to undergo apoptosis than wild-type T cells. Together, these features account for the decreased IL-2 secretion by in vitro-stimulated Jak3 -/-T cells. Overall, many of the lymphoid defects of Jak3-and ␥c-deficient mice can be accounted for by the lack of IL-7R and IL-2R signaling; however, other cytokine systems must also be involved in maintaining peripheral T cell homeostasis.

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“…However, because IL-7Ra-mediated signaling is indispensable for expression of the functional g-chain, gd T cells are completely absent in IL-7Ra 2/2 mice (Fig. 4A) (36,37). To circumvent this effect, we used the previously established system that gd T cell development in IL-7Ra 2/2 mice was rescued by introduction of a rearranged g-chain (38).…”

Section: Il-7ra-mediated Signaling Is Required For Homeostasis Of Il-mentioning

confidence: 99%

A Genome-Wide Analysis Identifies a Notch–RBP-Jκ–IL-7Rα Axis That Controls IL-17–Producing γδ T Cell Homeostasis in Mice

Nakamura

Shibata

Hatano

et al. 2015

The Journal of Immunology

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Notch signaling is an important regulator for the development and function of both αβ and γδ T cells, whereas roles of Notch signaling in T cell maintenance remain unclear. We reported previously that the Notch–Hes1 pathway was involved in the intrathymic development of naturally occurring IL-17–producing (IL-17+) γδ T cells. To gain insight into additional roles for the Notch axis in the homeostasis of γδ T cells, we performed a genome-wide analysis of Notch target genes and identified the novel promoter site of IL-7Rα driven by the Notch–RBP-Jκ pathway. Constitutive Notch signaling had the potential to induce IL-7Rα expression on γδ T cells in vivo, as well as in vitro, whereas conditional deletion of RBP-Jκ abrogated IL-7Rα expression, but not Hes1 expression, by γδ T cells and selectively reduced the pool size of IL-7Rαhigh IL-17+ γδ T cells in the periphery. In the absence of IL-7Rα–mediated signaling, IL-17+ γδ T cells were barely maintained in adult mice. Addition of exogenous IL-7 in vitro selectively expanded IL-17+ γδ T cells. Thus, our results revealed a novel role for the Notch–RBP-Jκ–IL-7Rα axis that is independent of Hes1 for homeostasis of IL-17+ γδ T cells.

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The V–J Recombination of T Cell Receptor-γ Genes Is Blocked in Interleukin-7 Receptor–deficient Mice

Cited by 124 publications

References 35 publications

Positive Effects of Glucocorticoids on T Cell Function by Up-Regulation of IL-7 Receptor α

Positive Effects of Glucocorticoids on T Cell Function by Up-Regulation of IL-7 Receptor α

T cell development and activation in Jak3-deficient mice

A Genome-Wide Analysis Identifies a Notch–RBP-Jκ–IL-7Rα Axis That Controls IL-17–Producing γδ T Cell Homeostasis in Mice

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