scholarly journals Neuropeptides Exert Direct Effects on Rat Thymic Epithelial Cells in Culture

1998 ◽  
Vol 6 (1-2) ◽  
pp. 95-104 ◽  
Author(s):  
Gail M. Head ◽  
R. Mentlein ◽  
Birte Von Patay ◽  
J. E.G. Downing ◽  
Marion D. Kendall

To determine if major thymic neuropeptides and neurotransmitters can directly influence the functional activity of cultured rat thymic epithelium, neuropeptides and neurotransmitters were applied, and intercellular communication, proliferation, and thymulin secretion assessed. After injections of a mixture of lucifer yellow dextran (too large to pass gap junctions) and cascade blue (which does) into single cells, some neuropeptides decrease dye coupling: 0.1 mM GABA (P< 0.0001), 100 nM NPY (P< 0.0001), 100 nM VIP (P< 0.001), 100 nM CGRP (P< 0.001), 100 nM SP (P< 0.01), and 0.1 mM histamine (P< 0.01), whereas 0.1 mM 5-HT, mM acetylcholine, and 1μM isoproterenol (β-adrenergic agonist) had no effect. Proliferation (incorporation of tritiated thymidine) was increased by CGRP (P= 0.004) and histamine (P< 0.02), but decreased by isoproterenol (P= 0.002), 5-HT (P= 0.003), and acetylcholine (P< 0.05). The percentage of multinucleate cells was decreased after isoproterenol (2.5%), and increased after 5-HT (21.3%), GABA (15%), and histamine (15.1%). Compared to controls, thymulin in the supernatant was decreased after challenge with acetylcholine (52%), isoproterenol (71%), 5-HT (73%), and histamine (84%). This study demonstrates direct effects of neuropeptides and neurotransmitters on functional aspects of cultured thymic epithelial cells.

1985 ◽  
Vol 33 (7) ◽  
pp. 687-694 ◽  
Author(s):  
J F Nicolas ◽  
W Savino ◽  
A Reano ◽  
J Viac ◽  
J Brochier ◽  
...  

The mouse thymic epithelial network was studied using three different anti-keratin antibodies. One of these antibodies, KL1, exclusively recognized a small subset of medullary epithelial cells characterized by its content of a high molecular weight keratin (63 kD). Since epithelial differentiation is known to be associated with the acquisition of high molecular weight keratins, KL1-positive cells, which express the Ia antigen and secrete thymulin, may represent a subset of highly differentiated cells among mouse thymic epithelial cells (TEC). These data reflect the heterogeneity of the thymic epithelium and support the concept that distinct TEC subsets might provide the thymus with different microenvironments.


Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 85-96 ◽  
Author(s):  
F. Serras ◽  
S. Fraser ◽  
C.M. Chuong

To study the pattern of gap junctional communication in chicken skin and feather development, we injected Lucifer Yellow into single cells and monitored the transfer of the fluorescent dye through gap junctions. Dye coupling is present between cells of the epithelium as well as between cells of the mesoderm. However, dye transfer did not occur equally in all directions and showed several consistent patterns and asymmetries, including: (1) no dye coupling between mesoderm and epithelium, (2) partial restriction of dye coupling at the feather bud/interbud boundary during early feather bud development, (3) preferential distribution of Lucifer Yellow along the anteroposterior axis of the feather placode and (4) absence of dye coupling in some epithelial cells. These results suggest the presence of preferential pathways of communication that may play a role in the patterning of chicken skin.


1989 ◽  
Vol 256 (3) ◽  
pp. C478-C485 ◽  
Author(s):  
C. J. Jones ◽  
P. M. Quinton

The dye-coupling status of secretory and reabsorptive cells in micro-dissected lengths of human eccrine sweat gland was investigated by means of intracellular microiontophoresis of the fluorescent naphthalimide dye Lucifer yellow CH (Mr 457), which passes through gap junctions. Cells of the reabsorptive duct exhibited complete dye coupling between the apical and basal layers of the epithelium. Conversely, cells of the secretory tubule exhibited selective dye coupling. Of the three cell types present, clear, dark, and myoepithelial, the dark cells were impaled and labeled almost exclusively in the present study. These cells were observed either as single cells or as dye-coupled groups of neighboring dark cells. In no instance were dark cells observed to be dye coupled to clear cells or to myoepithelial cells. Because myoepithelial cells are known to be dye coupled exclusively to neighboring myoepithelial cells, the remaining clear cells must either be uncoupled or show selective dye coupling to neighboring clear cells. The significance of these findings is considered with respect to the regulation and function of the different cell types present in the human eccrine sweat gland.


2005 ◽  
Vol 202 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Geoffrey O. Gillard ◽  
Andrew G. Farr

Medullary thymic epithelial cells (mTECs) express a broad spectrum of tissue- restricted self-antigens (TRAs), which are required for the development of central tolerance. A new study suggests that TRA expression is a specialized property of terminally differentiated mTECs. However, as discussed here, an alternative model—whereby TRA expression is regulated by conserved developmental programs active in developing mTECs—may be equally plausible.


1990 ◽  
Vol 1 (2) ◽  
pp. 67-75 ◽  
Author(s):  
Miodrag Čolić ◽  
Suzana Jovanović ◽  
Milijana Vasiljevski ◽  
Aleksandar Dujić

Ontogenetic study on the expression of cytokeratin (CK) polypeptides within particular subsets of rat thymic epithelial cells (TEC) has been performed by a large panel of anti-CK monoclonal antibodies (mAbs) using the streptavidin-biotin immunoperoxidase method. Simultaneous presence of two or more CK subunits in the same TEC has been demonstrated by double immunoflouorescence labeling. The obtained results showed that the expression of CK polypeptides in fetal and neonatal thymus differed from the adult patterns. The main difference was observed in expression of CK10, 18, and 19 polypeptides. During fetal ontogeny, CK10 and 18 are markers for most medullary TEC or a subset of medullary TEC, respectively, whereas CK19 is mainly a pan-TEC marker. In the adult animals, they are localized in the cortical and a subset of medullary TEC (CK18), subcapsular/perivascular and some medullary TEC (CK19), or in a subset of medullary TEC and Hasall’s corpuscles (HC) (CK10). The switch in their expression in the cortex was observed during the first two weeks of postnatal life.


2020 ◽  
Vol 21 (16) ◽  
pp. 5765
Author(s):  
Marta Figueiredo ◽  
Rita Zilhão ◽  
Hélia Neves

The thymus generates central immune tolerance by producing self-restricted and self-tolerant T-cells as a result of interactions between the developing thymocytes and the stromal microenvironment, mainly formed by the thymic epithelial cells. The thymic epithelium derives from the endoderm of the pharyngeal pouches, embryonic structures that rely on environmental cues from the surrounding mesenchyme for its development. Here, we review the most recent advances in our understanding of the molecular mechanisms involved in early thymic organogenesis at stages preceding the expression of the transcription factor Foxn1, the early marker of thymic epithelial cells identity. Foxn1-independent developmental stages, such as the specification of the pharyngeal endoderm, patterning of the pouches, and thymus fate commitment are discussed, with a special focus on epithelial–mesenchymal interactions.


1983 ◽  
Vol 157 (3) ◽  
pp. 907-920 ◽  
Author(s):  
B F Haynes ◽  
M Robert-Guroff ◽  
R S Metzgar ◽  
G Franchini ◽  
V S Kalyanaraman ◽  
...  

Using monoclonal antibody 12/1-2 against a 19,000-dalton human T cell leukemia virus (HTLV) protein (anti-p19), previously demonstrated to be reactive with HTLV-infected human cells, but not in numerous other uninfected cells, we found a reactive antigen to be expressed on the neuroendocrine component of human thymic epithelial cells but not on any other normal epithelial or neuroendocrine human tissues. Moreover, this reactive antigen is acquired on neuroendocrine thymic epithelium during thymic ontogeny--first appearing on fetal thymic epithelial cells between 8 and 15 wk gestation. While only a portion of thymic epithelial cells in the subcapsular cortical region of 15- and 24-wk fetal thymuses contained anti-p19+ epithelial cells, the entire subcapsular cortical region of newborn thymus epithelium was anti-p19+. By age 3 yr, normal subjects' entire subcapsular cortical and medullary thymic epithelium was anti-p19+. Using antibody against HTLV core protein, p24, and c-DNA probes for HTLV DNA, neither HTLV-specific p24 protein nor proviral DNA could be demonstrated in anti-p19+ thymic epithelial tissue. However, thymic epithelial extracts, disrupted HTLV extracts, as well as purified HTLV p19 antigen all inhibited the binding of anti-p19 antibody to thymic epithelium. Thus, anti-p19 may recognize a determinant on an HTLV-encoded 19,000-dalton structural protein that is shared by human thymic epithelium. Alternatively, anti-p19 defines a host encoded protein that is selectively expressed by normal thymic epithelium, and is induced to be expressed in HTLV-infected malignant T cells.


2007 ◽  
Vol 204 (3) ◽  
pp. 475-480 ◽  
Author(s):  
Adrian Liston ◽  
Andrew G. Farr ◽  
Zhibin Chen ◽  
Christophe Benoist ◽  
Diane Mathis ◽  
...  

Foxp3 is essential for the commitment of differentiating thymocytes to the regulatory CD4+ T (T reg) cell lineage. In humans and mice with a genetic Foxp3 deficiency, absence of this critical T reg cell population was suggested to be responsible for the severe autoimmune lesions. Recently, it has been proposed that in addition to T reg cells, Foxp3 is also expressed in thymic epithelial cells where it is involved in regulation of early thymocyte differentiation and is required to prevent autoimmunity. Here, we used genetic tools to demonstrate that the thymic epithelium does not express Foxp3. Furthermore, we formally showed that genetic abatement of Foxp3 in the hematopoietic compartment, i.e. in T cells, is both necessary and sufficient to induce the autoimmune lesions associated with Foxp3 loss. In contrast, deletion of a conditional Foxp3 allele in thymic epithelial cells did not result in detectable changes in thymocyte differentiation or pathology. Therefore, in mice the only known role for Foxp3 remains promotion of T reg cell differentiation within the T cell lineage, whereas there is no role for Foxp3 in thymic epithelial cells.


2002 ◽  
Vol 76 (13) ◽  
pp. 6415-6424 ◽  
Author(s):  
Pierre-Olivier Vidalain ◽  
David Laine ◽  
Yona Zaffran ◽  
Olga Azocar ◽  
Christine Servet-Delprat ◽  
...  

ABSTRACT In the thymus, epithelial cells comprise a heterogeneous population required for the generation of functional T lymphocytes, suggesting that thymic epithelium disruption by viruses may compromise T-cell lymphopoiesis in this organ. In a previous report, we demonstrated that in vitro, measles virus induced differentiation of cortical thymic epithelial cells as characterized by (i) cell growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as a final step of this process. In the present report, we have analyzed the mechanisms involved. First, measles virus-induced differentiation of thymic epithelial cells is shown to be strictly dependent on beta interferon (IFN-β) secretion. In addition, transfection with double-stranded RNA, a common intermediate of replication for a broad spectrum of viruses, is reported to similarly mediate thymic epithelial cell differentiation through IFN-β induction. Finally, we demonstrated that recombinant IFN-α, IFN-β, or IFN-γ was sufficient to induce differentiation and apoptosis of uninfected thymic epithelial cells. These observations suggested that interferon secretion by either infected cells or activated leukocytes, such as plasmacytoid dendritic cells or lymphocytes, may induce thymic epithelium disruption in a pathological context. Thus, we have identified a new mechanism that may contribute to thymic atrophy and altered T-cell lymphopoiesis associated with many infections.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Minwen Xu ◽  
Xiaoli Zhang ◽  
Ruiyun Hong ◽  
Dong-Ming Su ◽  
Liefeng Wang

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.


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