Studies on thymic epithelial cells in vitro

Anderson, Kim L.; Moore, Nel C.; McLoughlin, D.E.; Jenkinson, Eric J.; Owen, J. J. T.

doi:10.1016/s0145-305x(98)00011-1

Cited by 40 publications

(24 citation statements)

References 30 publications

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“…Earlier reports using RT-PCR showed that IL-7 is expressed by MHC class II-positive TECs, but the intrathymic localization of IL-7-expressing TECs was not determined (12,20,53). Most notably, the medulla contains the highest concentration of IL-7-expressing cells in the adult thymus, whereas IL-7-expressing TECs are sparsely distributed in the cortical and subcapsular regions.…”

Section: Discussionmentioning

confidence: 94%

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: 94%

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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“…Although a 3-dimensional organization of TEC is required for maintenance of Foxn1 expression, upstream signals/ factors that regulate expression of Foxn1 during thymic organogenesis and in postnatal thymus remain elusive. 17,18 It has been suggested that members of the Wnt glycoprotein family can regulate expression of Foxn1 in vitro. 19 In hair follicles, BMP4 has been shown to up-regulate Foxn1 expression.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells

Zook

Krishack

Zhang³

et al. 2011

Blood

124

134

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The forkhead box n1 (Foxn1) transcription factor is essential for thymic organogenesis during embryonic development; however, a functional role of Foxn1 in the postnatal thymus is less well understood. We developed Foxn1 transgenic mice (Foxn1Tg), in which overexpression of Foxn1 is driven by the human keratin-14 promoter. Expression of the Foxn1 transgene increased the endogenous Foxn1 levels. In aged mice, overexpression of Foxn1 in the thymus attenuated the decline in thymocyte numbers, prevented the decline in frequency of early thymic progenitors, and generated a higher number of signal joint TCR excised circle. Histologic studies revealed that structural alterations associated with thymic involution were diminished in aged Foxn1 Tg.

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“…In support of the last idea, it has been shown that monolayer culture conditions cause alterations in gene expression by purified major histocompatibility complex (MHC) class II + thymic epithelial cells and an irreversible loss of the functional ability of these cells to support thymocyte maturation. 32,33 In this regard, it might be interesting to investigate the effect of expressing transfected Spatial in thymic epithelial cells grown in a monolayer culture system. Spatial expression is also inducible in the LN in response to an immune challenge (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Spatial, a gene expressed in thymic stromal cells, depends on three-dimensional thymus organization for its expression

2000

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Although the importance of thymic stroma in thymopoiesis has been recognized, the underlying molecular details regarding stromal cell biology remain obscure. To study this area, we have cloned genes expressed in thymic stromal cells. Spatial is alternatively spliced to generate two mRNAs in thymus and lymph node (LN) but it is not expressed in the spleen. In mouse embryos, the short form begins expression at day 10 while the long form is not detected until day 12. Both mRNAs encode proline rich proteins and their closest homology is to homeobox and POU domain transcription factors. Spatial is not expressed in thymocytes, but it is expressed in 2-deoxyguanosine-treated day 14 fetal thymic organ culture (FTOC) and in reaggregated FTOC. These data suggest that a normal three-dimensional organization of stromal cells is required for Spatial expression. An antiserum raised against a C-terminal peptide detected proteins of 38 and 32 kDa in Western blots of total thymus proteins. In frozen thymus sections, subcapsular epithelial cells were stained with the anti-Spatial antiserum. Paracortical subcapsular cells of unknown function were also stained in the LN. Both forms of Spatial fused to the green fluorescent protein (GFP) localize to the nucleus in transfected cells. Genes and Immunity (2000) 1, 391-401.

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Studies on thymic epithelial cells in vitro

Cited by 40 publications

References 30 publications

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

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

Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells

Spatial, a gene expressed in thymic stromal cells, depends on three-dimensional thymus organization for its expression

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