Projects per year
Abstract
Members of the Wnt family of secreted glyco-lipo-proteins affect intrathymic T-cell development and are abundantly secreted by thymic epithelial cells (TECs) that create the specific microenvironment for thymocytes to develop into mature T-cells. During ageing, Wnt expression declines allowing adipoid involution of the thymic epithelium leading to reduced naive T-cell output. The protein kinase C (PKC) family of serine-threonine kinases is involved in numerous intracellular biochemical processes, including Wnt signal transduction. In the present study. PKC delta expression is shown to increase with age and to co-localise with Wnt receptors Frizzled (Fz)-4 and -6. It is also demonstrated that connective tissue growth factor (CTGF) is a Wnt-4 target gene and is potentially involved in a negative feed-back loop of Wnt signal regulation. Down-regulation of Wnt-4 expression and activation of multiple repressor pathways suppressing beta-catenin dependent signalling in TECs contribute to the initiation of thymic senescence. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
Original language | English |
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Pages (from-to) | 249-256 |
Number of pages | 8 |
Journal | Mechanisms of Ageing and Development |
Volume | 132 |
Issue number | 5 |
DOIs | |
Publication status | Published - 1 May 2011 |
Keywords
- PKC delta
- Thymic epithelium
- Wnt signalling
- Thymic atrophy
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Dive into the research topics of 'Multiple suppression pathways of canonical Wnt signalling control thymic epithelial senescence'. Together they form a unique fingerprint.Projects
- 1 Finished
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Generation of Intrathymic Microenvironments to Establish T-Cell Tolerance
Anderson, G., Jenkinson, E. & Lane, P.
1/10/10 → 30/09/15
Project: Research Councils