scholarly journals Modulation of Cytokeratin Expression in The Hamster Thymus: Evidence For a Plasticity of The Thymic Epithelium

1993 ◽  
Vol 3 (2) ◽  
pp. 137-146 ◽  
Author(s):  
Lucia Renata Meireles De Souza ◽  
Wilson Savino
Keyword(s):  
Distribution Pattern ◽  
Hormone Treatment ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelium ◽  
Mouse Thymus ◽  
Glucocorticoid Hormone ◽  
Cytokeratin Expression ◽  
Interspecific Diversity ◽  
Thymus Ontogeny

Cytokeratin (CK) expression was investigated, by means of immunocytochemistry, in the hamster thymic epithelium during ontogeny, as well as in primary cultures and upon glucocorticoid hormone treatmentin vivo. As compared to the distribution pattern of distinct monoclonal antibody-defined cytokeratins in the normal adult thymus, CK modulation was evidenced in the three situations studied. During thymus ontogeny, both cytokeratins of simple lining epithelia, as CK8 and CK18, as well as the CK1/CK10 pair (typical marker of terminal stage of keratinization), were expressed since early stages of thymus development. They were located in the central region of thymic lobules preceding the cortical-medullary distinctions. This differed from what had been previously shown for mouse thymus ontogeny, revealing that the interspecific diversity in the distribution pattern of thymic cytokeratins occurred early in fetal life. A modulation of CK expression was also detected when hamster thymic epithelial cells (TEC) were led to grow in culture, with a down-regulation of CK19 contrasting with an enhancement of CK18 expression. This diverged from the maintenance of thein situpattern when human TEC were cultured. Last,in vivohydrocortisone treatment, known to increase the numbers of KL1+cells in the mouse thymus medulla, promoted a cortical expression of the CK1/CK10 pair in the hamster thymus. Taken together, our findings demonstrate a continuous plasticity of the thymic epithelium, at least regarding cytokeratin expression, and enlarge the concept of interspecific diversity of intrathymic CK distribution in conditions as morphogenesis,in vitrosystem, and responsiveness to glucocorticoid hormone treatment.

scholarly journals Developmental studies on expression of monoclonal antibody-defined cytokeratins by thymic epithelial cells from normal and autoimmune mice.

1988 ◽  
Vol 36 (9) ◽  
pp. 1123-1129 ◽  
Author(s):  
W Savino ◽  
M Dardenne
Keyword(s):  
Monoclonal Antibodies ◽  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
High Dose ◽  
Fetal Life ◽  
Developmental Studies ◽  
Complex Products ◽  
Histocompatibility Complex ◽  
Cytokeratin Expression

A major component of the thymic microenvironment is a network of thymic epithelial cells (TEC) which are able to express class II major histocompatibility complex products and to secrete thymic hormones. In the present investigation, we used a panel of anti-cytokeratin (CK) antibodies to establish distinct cytokeratin-defined TEC subsets. Four subpopulations were identified. One, in the cortex, is defined by anti-CK8 and anti-CK18 monoclonal antibodies (MAb). The other three subsets are medullary, two minor ones respectively reactive with anti-CK19 and KL1 monoclonal antibodies (the latter being specific for CK3 and 10), and a major one characterized by negative reaction with the above-mentioned MAb but strongly positive after labeling with a polyclonal (and polyspecific) anti-keratin immunoserum. Ontogenetic studies revealed that the CK8+/18+ TEC subset is the first to be detected in fetal life. Moreover, the numbers of CK3/10+ cells and CK19+ cells decrease in aging normal mice, a phenomenon that seems to occur early in autoimmune mice. We also observed that these two medullary TEC subsets are sensitive to high-dose in vivo treatment with hydrocortisone, which stimulates a dramatic increase in CK3/10+ cells and a certain decrease in CK19+ cells. Our results indicate that a number of mouse TEC subsets can be distinguished by cytokeratin expression. Such a strategy can be applied to analyze TEC sensitivity to drugs and might also be useful to further understanding of differential TEC function regarding intrathymic T-cell differentiation.

scholarly journals Is There an Interspecific Diversity of the Thymic Microenvironment?

1993 ◽  
Vol 3 (2) ◽  
pp. 123-135 ◽  
Author(s):  
Lucia Renata Meireles de Souza ◽  
Valeria Trajano ◽  
Wilson Savino
Keyword(s):  
Extracellular Matrix ◽  
Monoclonal Antibodies ◽  
Comparative Study ◽  
Mammalian Species ◽  
Thymic Epithelial Cells ◽  
General Phenomenon ◽  
Thymic Epithelium ◽  
Extracellular Matrix Components ◽  
Matrix Components ◽  
Interspecific Diversity

Thymic epithelial cells (TEC) heterogeneity suggests the existence of functional subsets. Anti-cytokeratin (Anti-CK) monoclonal antibodies (MAb), markers of epithelial differentiation, have been used to detect TEC subsets in rodents and humans. These MAb revealed a different topography of CK-defined TEC subsets in mice and humans, leading us to carry out a comparative study of mammalian thymuses. Our study showed that the distribution pattern of cytokeratins in the thymic epithelium is complex and unique, with coexpression of CK typical of simple and stratified epithelia. Moreover, we demonstrated an interspecific diversity of CK expression within the thymic lobules. Interestingly, such diversity was not a general phenomenon for the expression of any thymic microenvironmental proteins, because the location of extracellular matrix components was essentially similar in the mammalian species studied.

scholarly journals Effect of Coxsackievirus B4 Infection on the Thymus: Elucidating Its Role in the Pathogenesis of Type 1 Diabetes

2021 ◽  
Vol 9 (6) ◽  
pp. 1177
Author(s):  
Abdulaziz Alhazmi ◽  
Magloire Pandoua Nekoua ◽  
Hélène Michaux ◽  
Famara Sane ◽  
Aymen Halouani ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Viral Infections ◽  
Lymphoid Organ ◽  
Thymic Epithelial Cells ◽  
Central Tolerance ◽  
Coxsackievirus B4

The thymus gland is a primary lymphoid organ for T-cell development. Various viral infections can result in disturbance of thymic functions. Medullary thymic epithelial cells (mTECs) are important for the negative selection of self-reactive T-cells to ensure central tolerance. Insulin-like growth factor 2 (IGF2) is the dominant self-peptide of the insulin family expressed in mTECs and plays a crucial role in the intra-thymic programing of central tolerance to insulin-secreting islet β-cells. Coxsackievirus B4 (CVB4) can infect and persist in the thymus of humans and mice, thus hampering the T-cell maturation and differentiation process. The modulation of IGF2 expression and protein synthesis during a CVB4 infection has been observed in vitro and in vivo in mouse models. The effect of CVB4 infections on human and mouse fetal thymus has been studied in vitro. Moreover, following the inoculation of CVB4 in pregnant mice, the thymic function in the fetus and offspring was disturbed. A defect in the intra-thymic expression of self-peptides by mTECs may be triggered by CVB4. The effects of viral infections, especially CVB4 infection, on thymic cells and functions and their possible role in the pathogenesis of type 1 diabetes (T1D) are presented.

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
Keyword(s):  
Epithelial Cells ◽  
Lucifer Yellow ◽  
Tritiated Thymidine ◽  
Single Cells ◽  
Thymic Epithelial Cells ◽  
Dye Coupling ◽  
Direct Effects ◽  
Adrenergic Agonist ◽  
Thymic Epithelium ◽  
Functional Aspects

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.

Activated protein C targets immune cells and rheumatoid synovial fibroblasts to prevent inflammatory arthritis in mice

Rheumatology ◽  
2019 ◽  
Vol 58 (10) ◽  
pp. 1850-1860 ◽  
Author(s):  
Meilang Xue ◽  
Suat Dervish ◽  
Kelly J McKelvey ◽  
Lyn March ◽  
Fang Wang ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Synovial Fibroblasts ◽  
Endothelial Protein C Receptor ◽  
Mouse Thymus ◽  
Tnf Α ◽  
Thymus Cells ◽  
Proliferation And Invasion

Abstract Objectives To investigate whether activated protein C (APC), a physiological anticoagulant can inhibit the inflammatory/invasive properties of immune cells and rheumatoid arthritis synovial fibroblasts (RASFs) in vitro and prevent inflammatory arthritis in murine antigen-induced arthritis (AIA) and CIA models. Methods RASFs isolated from synovial tissues of patients with RA, human peripheral blood mononuclear cells (PBMCs) and mouse thymus cells were treated with APC or TNF-α/IL-17 and the following assays were performed: RASF proliferation and invasion by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cell invasion assays, respectively; cytokines and signalling molecules using ELISA or western blot; Th1 and Th17 phenotypes in human PBMCs or mouse thymus cells by flow cytometry. The in vivo effect of APC was evaluated in AIA and CIA models. Results In vitro, APC inhibited IL-1β, IL-17 and TNF-α production, IL-17-stimulated cell proliferation and invasion and p21 and nuclear factor κB activation in RASFs. In mouse thymus cells and human PBMCs, APC suppressed Th1 and Th17 phenotypes. In vivo, APC inhibited pannus formation, cartilage destruction and arthritis incidence/severity in both CIA and AIA models. In CIA, serum levels of IL-1β, IL-6, IL-17, TNF-α and soluble endothelial protein C receptor were significantly reduced by APC treatment. Blocking endothelial protein C receptor, the specific receptor for APC, abolished the early or preventative effect of APC in AIA. Conclusion APC prevents the onset and development of arthritis in CIA and AIA models via suppressing inflammation, Th1/Th17 phenotypes and RASF invasion, which is likely mediated via endothelial protein C receptor.

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