Upregulated Expression of Fibronectin Receptors Underlines the Adhesive Capability of Thymocytes to Thymic Epithelial Cells During the Early Stages of Differentiation: Lessons From Sublethally Irradiated Mice

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 974-990
Author(s):  
Sergio R. Dalmau ◽  
Claudia S. Freitas ◽  
Wilson Savino
Keyword(s):  
Epithelial Cells ◽  
Cell Attachment ◽  
Whole Body ◽  
Thymic Epithelial Cells ◽  
Strongly Correlated ◽  
Enhanced Expression ◽  
Single Positive ◽  
Young Stage ◽  
And Function

A 250-cGy whole-body γ-radiation dose was used to induce thymus regression in mice, and to study the expression and function of extracellular matrix (ECM) receptors in distinct thymocyte subsets emerging during repopulation of the organ. The onset of regeneration was detected from day 2 to 3 postirradiation (P-Ir), when a remarkable increase in the absolute counts of CD3−CD25hiCD44+ and CD3−CD25in/hiCD44−cells occurred. Enhanced expression of L-selectin, 4, and 5 integrin chains (L-selhi 4hi5hi) was also exhibited by these cells. This pattern of expression was maintained until the CD4+CD8+ (DP) young stage was achieved. Afterward, there was a general downregulation of these ECM receptors in DP as well as in CD4+ or CD8+ single positive (SP) thymocytes (L-selin 4in5in). In some recently generated SP cells, 4 expression was downregulated before the 5 chain, and L-selectin was upregulated in half of more mature cells. The expression of the 6 integrin chain was downregulated only in maturing CD4+cells. Importantly, the increased expression of L-selectin and 4 and 5 chains in thymocytes was strongly correlated with their adhesiveness to thymic epithelial cells (TEC) in vitro. Blocking experiments with monoclonal antibody or peptides showed the following: (1) that the LDV rather than the REDV cell attachment motif in the IIIC segment of fibronectin is targeted by the 4 integrin during thymocyte/TEC adhesion; (2) that the RGD motif of the 120-kD fragment of fibronectin, a target for 5 integrin, has a secondary role in this adhesion; and (3) that the YIGSR cell attachment motif of the β1 chain of laminin/merosin recognized by a nonintegrin receptor is not used for thymocyte adherence. In conclusion, our results show that an upregulated set of receptors endows CD25+ precursors and cells up to the young DP stage with a high capability of interacting with thymic ECM components.

Upregulated Expression of Fibronectin Receptors Underlines the Adhesive Capability of Thymocytes to Thymic Epithelial Cells During the Early Stages of Differentiation: Lessons From Sublethally Irradiated Mice

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 974-990 ◽  
Author(s):  
Sergio R. Dalmau ◽  
Claudia S. Freitas ◽  
Wilson Savino
Keyword(s):  
Epithelial Cells ◽  
Cell Attachment ◽  
Whole Body ◽  
Thymic Epithelial Cells ◽  
Strongly Correlated ◽  
Enhanced Expression ◽  
Single Positive ◽  
Young Stage ◽  
And Function

Abstract A 250-cGy whole-body γ-radiation dose was used to induce thymus regression in mice, and to study the expression and function of extracellular matrix (ECM) receptors in distinct thymocyte subsets emerging during repopulation of the organ. The onset of regeneration was detected from day 2 to 3 postirradiation (P-Ir), when a remarkable increase in the absolute counts of CD3−CD25hiCD44+ and CD3−CD25in/hiCD44−cells occurred. Enhanced expression of L-selectin, 4, and 5 integrin chains (L-selhi 4hi5hi) was also exhibited by these cells. This pattern of expression was maintained until the CD4+CD8+ (DP) young stage was achieved. Afterward, there was a general downregulation of these ECM receptors in DP as well as in CD4+ or CD8+ single positive (SP) thymocytes (L-selin 4in5in). In some recently generated SP cells, 4 expression was downregulated before the 5 chain, and L-selectin was upregulated in half of more mature cells. The expression of the 6 integrin chain was downregulated only in maturing CD4+cells. Importantly, the increased expression of L-selectin and 4 and 5 chains in thymocytes was strongly correlated with their adhesiveness to thymic epithelial cells (TEC) in vitro. Blocking experiments with monoclonal antibody or peptides showed the following: (1) that the LDV rather than the REDV cell attachment motif in the IIIC segment of fibronectin is targeted by the 4 integrin during thymocyte/TEC adhesion; (2) that the RGD motif of the 120-kD fragment of fibronectin, a target for 5 integrin, has a secondary role in this adhesion; and (3) that the YIGSR cell attachment motif of the β1 chain of laminin/merosin recognized by a nonintegrin receptor is not used for thymocyte adherence. In conclusion, our results show that an upregulated set of receptors endows CD25+ precursors and cells up to the young DP stage with a high capability of interacting with thymic ECM components.

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro

2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Progenitor Cells ◽  
Thymic Epithelial Cells ◽  
Erythroid Progenitor ◽  
Term Survival ◽  
Long Term Survival ◽  
Erythroid Progenitor Cells

scholarly journals Modulation of IGF2 Expression in the Murine Thymus and Thymic Epithelial Cells Following Coxsackievirus-B4 Infection

2021 ◽  
Vol 9 (2) ◽  
pp. 402
Author(s):  
Hélène Michaux ◽  
Aymen Halouani ◽  
Charlotte Trussart ◽  
Chantal Renard ◽  
Hela Jaïdane ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Line ◽  
Thymic Epithelial Cells ◽  
Altered Expression ◽  
Coxsackievirus B4 ◽  
Gene Coding ◽  
Self Tolerance ◽  
Stat3 Phosphorylation ◽  
The Stability

Coxsackievirus B4 (CV-B4) can infect human and murine thymic epithelial cells (TECs). In a murine TEC cell line, CV-B4 can downregulate the transcription of the insulin-like growth factor 2 (Igf2) gene coding for the self-peptide of the insulin family. In this study, we show that CV-B4 infections of a murine TEC cell line decreased Igf2 P3 promoter activity by targeting a region near the transcription start site; however, the stability of Igf2 transcripts remained unchanged, indicating a regulation of Igf2 transcription. Furthermore, CV-B4 infections decreased STAT3 phosphorylation in vitro. We also showed that mice infected with CV-B4 had an altered expression of Igf2 isoforms as detected in TECs, followed by a decrease in the pro-IGF2 precursor in the thymus. Our study sheds new light on the intrathymic regulation of Igf2 transcription during CV-B4 infections and supports the hypothesis that a viral infection can disrupt central self-tolerance to insulin by decreasing Igf2 transcription in the thymic epithelium.

Effects of 2,3,7,8-TCDD and PCB 126 on human thymic epithelial cells in vitro

2003 ◽  
Vol 77 (6) ◽  
pp. 358-364 ◽  
Author(s):  
Kai Riecke ◽  
André Schmidt ◽  
Ralf Stahlmann
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Pcb 126

scholarly journals Human thymocytes bind to autologous and allogeneic thymic epithelial cells in vitro.

1986 ◽  
Vol 83 (17) ◽  
pp. 6588-6592 ◽  
Author(s):  
K. H. Singer ◽  
L. S. Wolf ◽  
D. F. Lobach ◽  
S. M. Denning ◽  
D. T. Tuck ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells

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.

In vitro growth and maintenance of two morphologically distinct populations of thymic epithelial cells

1985 ◽  
Vol 90 (2) ◽  
pp. 439-450 ◽  
Author(s):  
A.C. Nieburgs ◽  
P.T. Picciano ◽  
J.H. Korn ◽  
T. McCalister ◽  
C. Allred ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
In Vitro Growth

scholarly journals Expression of CA-125 by progestational bovine endometrium: prospective regulation and function

Reproduction ◽  
2003 ◽  
pp. 615-620 ◽  
Author(s):  
AC McDonnel ◽  
EA Van Kirk ◽  
KJ Austin ◽  
TR Hansen ◽  
EL Belden ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ovarian Cancer Cell Line ◽  
Amino Acid Content ◽  
Ca 125 ◽  
Embryonic Cells ◽  
Cancer Antigen 125 ◽  
Interferon Tau ◽  
Endometrial Cells ◽  
And Function

Cancer antigen 125 (CA-125) is expressed by malignant human ovarian surface epithelial cells and derivatives of the Mullerian duct system. This study explored the expression, regulation, and function of CA-125 in the bovine uterus. CA-125 was localized by immunohistochemistry to the apical surfaces of epithelial cells lining the endometrium and proximal glands of the late luteal phase and early pregnancy; antigen was not detected during oestrus or the postpartum period. Production of CA-125 by bovine endometrial cells in vitro was upregulated by progesterone and interferon-tau. Immunopurified CA-125 from uterine flushes of dioestrous or pregnant cows was similar in biochemical composition (as determined by gel electrophoresis and amino acid content) to the human antigen isolated from incubation medium conditioned by the ovarian cancer cell line OVCAR-3. Bovine CA-125 inhibited complement-induced lysis of antibody-sensitized sheep erythrocytes. It is suggested that endometrial CA-125 exerts a progestational role in part by protecting maternal and embryonic cells from immune targeting and lysis.

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