Identification of Transcription Factors Activated in Thymic Epithelial Cells During Embryonic Thymus Development

2014 ◽  
pp. 163-170
Author(s):  
Taishin Akiyama ◽  
Junwen Qin ◽  
Daisuke Ohshima ◽  
Jun-ichiro Inoue
Keyword(s):  
Transcription Factors ◽  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Thymus Development

scholarly journals Myc controls a distinct transcriptional program in fetal thymic epithelial cells that determines thymus growth

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jennifer E. Cowan ◽  
Justin Malin ◽  
Yongge Zhao ◽  
Mina O. Seedhom ◽  
Christelle Harly ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
T Cell Development ◽  
Thymic Epithelial Cells ◽  
Fetal Life ◽  
Ribosomal Biogenesis ◽  
Transcriptional Program ◽  
Fetal Thymus ◽  
Thymus Development ◽  
And Function ◽  
Thymus Size

AbstractInteractions between thymic epithelial cells (TEC) and developing thymocytes are essential for T cell development, but molecular insights on TEC and thymus homeostasis are still lacking. Here we identify distinct transcriptional programs of TEC that account for their age-specific properties, including proliferation rates, engraftability and function. Further analyses identify Myc as a regulator of fetal thymus development to support the rapid increase of thymus size during fetal life. Enforced Myc expression in TEC induces the prolonged maintenance of a fetal-specific transcriptional program, which in turn extends the growth phase of the thymus and enhances thymic output; meanwhile, inducible expression of Myc in adult TEC similarly promotes thymic growth. Mechanistically, this Myc function is associated with enhanced ribosomal biogenesis in TEC. Our study thus identifies age-specific transcriptional programs in TEC, and establishes that Myc controls thymus size.

scholarly journals Thymic Epithelial Cells Are a Nonredundant Source of Wnt Ligands for Thymus Development

2015 ◽  
Vol 195 (11) ◽  
pp. 5261-5271 ◽  
Author(s):  
F. Brunk ◽  
I. Augustin ◽  
M. Meister ◽  
M. Boutros ◽  
B. Kyewski
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Thymus Development ◽  
Wnt Ligands

Thymocyte Contact or Monoclonal Antibody-Mediated Clustering of 3β1 or 6β4 Integrins Activate Interleukin-6 (IL-6) Transcription Factors (NF-κB and NF-IL6) and IL-6 Production in Human Thymic Epithelial Cells

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3745-3755 ◽  
Author(s):  
Dunia Ramarli ◽  
Maria Teresa Scupoli ◽  
Emma Fiorini ◽  
Ornella Poffe ◽  
Monica Brentegani ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Epithelial Cells ◽  
Interleukin 6 ◽  
Intracellular Signaling ◽  
Dominant Role ◽  
Functional Differentiation ◽  
Lymphoid Cells ◽  
Serine Phosphorylation ◽  
Thymic Epithelial Cells ◽  
Nuclear Targeting

Abstract T-cell precursors develop within the thymus in contact with multiple supportive elements, among which thymic epithelial cells (TEC) are known to exert a dominant role in their homing, survival, and functional differentiation. All these functions are supported by cell-cell contacts and cytokine release. Signaling events triggered in lymphoid cells by adhesion to TEC are well characterized, but little is known about the opposite phenomenon. To address this issue, we derived cultures of TEC from human normal thymus. TEC monolayers were cocultured with thymocytes and immunostained with monoclonal antibodies (MoAbs) to integrin  (2, 3, 4, and 6) and β (β1 and β4) chains. Optical and confocal analysis showed that integrins were polarized on TEC at discrete surface locations: 6β4 lined the basal surface of TEC monolayers, whereas 3β1 was found mostly at TEC-TEC contacts; it is noteworthy that both 3β1 and 6β4 became highly enriched also at the boundaries with adherent thymocytes. Functional studies performed with MoAbs anti-β1 and -β4 integrins showed that β1, and, to a much lower extent, β4 heterodimers are involved in the TEC-thymocyte adhesion. Thymocyte contact or MoAb-mediated ligation of 3, 6, β1, and β4 integrins was investigated as a potential inducer of intracellular signaling in TEC. Thymocyte adhesion or cross-linking of MoAbs bound to integrins clustered at the TEC/thymocyte contact sites led to activation of interleukin-6 (IL-6) gene transcription factors, namely NF-IL6 serine phosphorylation and NF-κB nuclear targeting, as well as to increased IL-6 secretion. We propose that integrin clustering occurring during TEC-thymocyte contacts modulates in TEC the gene expression of a cytokine involved in thymocyte growth and functional differentiation.

Thymocyte Contact or Monoclonal Antibody-Mediated Clustering of 3β1 or 6β4 Integrins Activate Interleukin-6 (IL-6) Transcription Factors (NF-κB and NF-IL6) and IL-6 Production in Human Thymic Epithelial Cells

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3745-3755 ◽  
Author(s):  
Dunia Ramarli ◽  
Maria Teresa Scupoli ◽  
Emma Fiorini ◽  
Ornella Poffe ◽  
Monica Brentegani ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Epithelial Cells ◽  
Interleukin 6 ◽  
Intracellular Signaling ◽  
Dominant Role ◽  
Functional Differentiation ◽  
Lymphoid Cells ◽  
Serine Phosphorylation ◽  
Thymic Epithelial Cells ◽  
Nuclear Targeting

T-cell precursors develop within the thymus in contact with multiple supportive elements, among which thymic epithelial cells (TEC) are known to exert a dominant role in their homing, survival, and functional differentiation. All these functions are supported by cell-cell contacts and cytokine release. Signaling events triggered in lymphoid cells by adhesion to TEC are well characterized, but little is known about the opposite phenomenon. To address this issue, we derived cultures of TEC from human normal thymus. TEC monolayers were cocultured with thymocytes and immunostained with monoclonal antibodies (MoAbs) to integrin  (2, 3, 4, and 6) and β (β1 and β4) chains. Optical and confocal analysis showed that integrins were polarized on TEC at discrete surface locations: 6β4 lined the basal surface of TEC monolayers, whereas 3β1 was found mostly at TEC-TEC contacts; it is noteworthy that both 3β1 and 6β4 became highly enriched also at the boundaries with adherent thymocytes. Functional studies performed with MoAbs anti-β1 and -β4 integrins showed that β1, and, to a much lower extent, β4 heterodimers are involved in the TEC-thymocyte adhesion. Thymocyte contact or MoAb-mediated ligation of 3, 6, β1, and β4 integrins was investigated as a potential inducer of intracellular signaling in TEC. Thymocyte adhesion or cross-linking of MoAbs bound to integrins clustered at the TEC/thymocyte contact sites led to activation of interleukin-6 (IL-6) gene transcription factors, namely NF-IL6 serine phosphorylation and NF-κB nuclear targeting, as well as to increased IL-6 secretion. We propose that integrin clustering occurring during TEC-thymocyte contacts modulates in TEC the gene expression of a cytokine involved in thymocyte growth and functional differentiation.

scholarly journals Stabilized β-Catenin in Thymic Epithelial Cells Blocks Thymus Development and Function

2009 ◽  
Vol 182 (5) ◽  
pp. 2997-3007 ◽  
Author(s):  
Saulius Zuklys ◽  
Jason Gill ◽  
Marcel P. Keller ◽  
Mathias Hauri-Hohl ◽  
Saule Zhanybekova ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Thymus Development ◽  
And Function

scholarly journals MicroRNAs Regulate Thymic Epithelium in Age-Related Thymic Involution via Down- or Upregulation of Transcription Factors

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Minwen Xu ◽  
Xiaoli Zhang ◽  
Ruiyun Hong ◽  
Dong-Ming Su ◽  
Liefeng Wang
Keyword(s):  
Transcription Factors ◽  
Epithelial Cells ◽  
Regulatory Networks ◽  
Current Understanding ◽  
Untranslated Regions ◽  
Thymic Epithelial Cells ◽  
Thymic Involution ◽  
Thymic Function ◽  
Thymic Epithelium ◽  
Age Related

Age-related thymic involution is primarily induced by defects in nonhematopoietic thymic epithelial cells (TECs). It is characterized by dysfunction of multiple transcription factors (TFs), such as p63 and FoxN1, and also involves other TEC-associated regulators, such as Aire. These TFs and regulators are controlled by complicated regulatory networks, in which microRNAs (miRNAs) act as a key player. miRNAs can either directly target the 3′-UTRs (untranslated regions) of the TFs to suppress TF expression or target TF inhibitors to reduce or increase TF inhibitor expression and thereby indirectly enhance or inhibit TF expression. Here, we review the current understanding and recent studies about how miRNAs are involved in age-related thymic involution via regulation of TEC-autonomous TFs. We also discuss potential strategies for targeting miRNAs to rejuvenate age-related declined thymic function.

scholarly journals Differential Requirement for Mesenchyme in the Proliferation and Maturation of Thymic Epithelial Progenitors

2003 ◽  
Vol 198 (2) ◽  
pp. 325-332 ◽  
Author(s):  
William E. Jenkinson ◽  
Eric J. Jenkinson ◽  
Graham Anderson
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Function ◽  
Mesenchymal Cells ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Cell ◽  
Thymus Development ◽  
Cell Pool ◽  
Proliferation And Differentiation ◽  
Essential Prerequisite

Formation of a mature thymic epithelial microenvironment is an essential prerequisite for the generation of a functionally competent T cell pool. It is likely that recently identified thymic epithelial precursors undergo phases of proliferation and differentiation to generate mature cortical and medullary thymic microenvironments. The mechanisms regulating development of immature thymic epithelial cells are unknown. Here we provide evidence that expansion of embryonic thymic epithelium is regulated by the continued presence of mesenchyme. In particular, mesenchymal cells are shown to mediate thymic epithelial cell proliferation through their provision of fibroblast growth factors 7 and 10. In contrast, differentiation of immature thymic epithelial cells, including acquisition of markers of mature cortical and medullary epithelium, occurs in the absence of ongoing mesenchymal support. Collectively, our data define a role for mesenchymal cells in thymus development, and indicate distinct mechanisms regulate proliferation and differentiation of immature thymic epithelial cells. In addition, our findings may aid in studies aimed at developing strategies to enhance thymus reconstitution and functioning in clinical certain contexts where thymic epithelial cell function is perturbed.

scholarly journals Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 194
Author(s):  
Daniil Shevyrev ◽  
Valeriy Tereshchenko ◽  
Vladimir Kozlov ◽  
Sergey Sennikov
Keyword(s):  
Transcription Factors ◽  
Epithelial Cells ◽  
Adaptive Immunity ◽  
Adaptive Immune System ◽  
High Specificity ◽  
Structure Functions ◽  
The Self ◽  
T Cell Subsets ◽  
Thymic Epithelial Cells ◽  
Self Antigens

It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the “calibration” of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system.

Altered thymic epithelial cells may be decisive for Moloney virus-induced lymphoma development

1983 ◽  
Vol 41 ◽  
pp. 784-785
Author(s):  
U.I. Heine ◽  
G.R.F. Krueger ◽  
E. Munoz ◽  
A. Karpinski
Keyword(s):  
Epithelial Cells ◽  
Leukemia Virus ◽  
Light And Electron Microscopy ◽  
Tumor Development ◽  
Current Evidence ◽  
Thymic Epithelial Cells ◽  
Thymic Tissue ◽  
Newborn Mice ◽  
Moloney Leukemia Virus ◽  
Differentiation Block

Infection of newborn mice with Moloney leukemia virus (M-MuLV) causes a T-cell differentiation block in the thymic cortex accompanied by proliferation and accumulation of prethymic lymphoblasts in the thymus and subsequent spreading of these cells to generate systemic lymphoma. Current evidence shows that thymic reticular epithelial cells (REC) provide a microenvironment necessary for the maturation of prethymic lymphoblasts to mature T-lymphocytes by secretion of various thymic factors. A change in that environment due to infection of REC by virus could be decisive for the failure of lymphoblasts to mature and thus contribute to lymphoma development.We have studied the morphology and distribution of the major thymic cell populations at different stages of tumorigenesis in Balb/c mice infected when newborn with 0.2ml M-MuLV suspension, 6.8 log FFU/ml. Thymic tissue taken at 1-2 weekly intervals up to tumor development was processed for light and electron microscopy, using glutaraldehyde-OsO4fixation and Epon-Araldite embedding.

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