Is There an Interspecific Diversity of the Thymic Microenvironment?

Souza, Lucia Renata Meireles de; Trajano, Valéria da Silva; Savino, Wilson

doi:10.1155/1993/48056

Cited by 17 publications

(2 citation statements)

References 31 publications

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“…Fibronectin (FN) is one ECM ligand constitutively expressed in all mammalian thymuses so far analyzed, including mice and humans [ 6 - 8 ]. Particularly in the human thymus both FN isoforms were detected within the thymic lobules [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

RNA interference-mediated knockdown of CD49e (α5 integrin chain) in human thymic epithelial cells modulates the expression of multiple genes and decreases thymocyte adhesion

et al. 2010

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BackgroundThe thymus is a central lymphoid organ, in which bone marrow-derived T cell precursors undergo a complex process of maturation. Developing thymocytes interact with thymic microenvironment in a defined spatial order. A component of thymic microenvironment, the thymic epithelial cells, is crucial for the maturation of T-lymphocytes through cell-cell contact, cell matrix interactions and secretory of cytokines/chemokines. There is evidence that extracellular matrix molecules play a fundamental role in guiding differentiating thymocytes in both cortical and medullary regions of the thymic lobules. The interaction between the integrin α5β1 (CD49e/CD29; VLA-5) and fibronectin is relevant for thymocyte adhesion and migration within the thymic tissue. Our previous results have shown that adhesion of thymocytes to cultured TEC line is enhanced in the presence of fibronectin, and can be blocked with anti-VLA-5 antibody.ResultsHerein, we studied the role of CD49e expressed by the human thymic epithelium. For this purpose we knocked down the CD49e by means of RNA interference. This procedure resulted in the modulation of more than 100 genes, some of them coding for other proteins also involved in adhesion of thymocytes; others related to signaling pathways triggered after integrin activation, or even involved in the control of F-actin stress fiber formation. Functionally, we demonstrated that disruption of VLA-5 in human TEC by CD49e-siRNA-induced gene knockdown decreased the ability of TEC to promote thymocyte adhesion. Such a decrease comprised all CD4/CD8-defined thymocyte subsets.ConclusionConceptually, our findings unravel the complexity of gene regulation, as regards key genes involved in the heterocellular cell adhesion between developing thymocytes and the major component of the thymic microenvironment, an interaction that is a mandatory event for proper intrathymic T cell differentiation.

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Section: Introductionmentioning

confidence: 99%

RNA interference-mediated knockdown of CD49e (α5 integrin chain) in human thymic epithelial cells modulates the expression of multiple genes and decreases thymocyte adhesion

et al. 2010

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“…Inclusion of ectodermal cells into the developing thymus would help to explain some of the heterogeneity of epithelial cells that occupy the mature thymus. In the epithelial stroma of the thymus, subsets of cells, as identified by antigenic markers, occur within a species and differ somewhat among species (Desouza and Savino, 1993;Paz et al, 1993).…”

Section: Expansion Of Pharyngeal Pouchesmentioning

confidence: 99%

Development of the thymus

Bockman

1997

Microsc. Res. Tech.

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Proper development of the thymus is critical for an individual to acquire full immune capability. A full complement of the components that participate in thymic development, interacting with each other at the correct time, is required for maturation. In order to establish the microenvironment necessary for T‐cell differentiation, the epithelial primordium of the thymus must expand from pharyngeal endoderm with the aid of contributions from the ectoderm. Experimental studies have established the importance of mesenchymal derivatives from the neural crest in functional development of the epithelial primordium. Interfering with this process inhibits thymic development in a manner similar to that observed in congenital conditions such as the DiGeorge syndrome and the fetal alcohol syndrome. These observations provide clues to understanding the origin of defects in thymus‐dependent immunity, and point the way to studies that will expand our understanding of the controls that are involved in genetic and environmental factors impacting on this process. Microsc. Res. Tech. 38:209–215, 1997. © 1997 Wiley‐Liss, Inc.

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Heterogeneity of epithelial cells in the rat thymus

Waal

Rademakers²

1997

Microsc. Res. Tech.

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The morphological heterogeneity of the thymic epithelium has been well documented both at the light and electron microscopic level. Immunohistochemistry has revealed four broad classes of epithelial cells (EC): subcapsule/perivascular, cortical, medullary EC, and medullary Hassall's corpuscles. Ultrastructural analysis has revealed further heterogeneity. In the cortex, four EC subtypes have been described ultrastructurally: subcapsular/perivascular, “pale,” “intermediate,” and “dark” EC. These subtypes are also present in the medulla. Two additional EC subtypes are restricted to the medulla: an undifferentiated subtype, and a subtype displaying signs of high metabolic activity. Based on the morphological features of the epithelium, it has been hypothetized that the thymic EC subtypes represent a process of differentiation. Microsc. Res. Tech. 38:227–236, 1997. © 1997 Wiley‐Liss, Inc.

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Is There an Interspecific Diversity of the Thymic Microenvironment?

Cited by 17 publications

References 31 publications

RNA interference-mediated knockdown of CD49e (α5 integrin chain) in human thymic epithelial cells modulates the expression of multiple genes and decreases thymocyte adhesion

RNA interference-mediated knockdown of CD49e (α5 integrin chain) in human thymic epithelial cells modulates the expression of multiple genes and decreases thymocyte adhesion

Development of the thymus

Heterogeneity of epithelial cells in the rat thymus

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