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Transforming growth factor-β signaling in thymic epithelial cells : its role in development, steady-state and immune reconstitution

Hauri-Hohl, Mathias Martin. Transforming growth factor-β signaling in thymic epithelial cells : its role in development, steady-state and immune reconstitution. 2010, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_9129

Abstract

The thymus constitutes the primary lymphoid organ responsible for the generation of naïve T cells. Its stromal compartment is composed of a scaffold of different subsets of epithelial cells that provide soluble and membrane-bound molecules essential for thymocyte maturation and selection. With senescence, a steady decline in the thymic output of T cells has been observed. Numeric and qualitative changes in the stromal compartment of the thymus resulting in reduced thymopoietic capacity have been suggested to account for this physiological process. The precise cellular and molecular mechanisms underlying thymic senescence are, however, only incompletely understood. Here, we demonstrate that TGF-beta signaling in thymic epithelial cells exerts a direct influence on the cell’s capacity to support thymopoiesis in the aged mouse as the physiological process of thymic senescence is mitigated in mice deficient for the expression of TGF-beta receptor type II on thymic epithelial cells. Moreover, TGF-beta signaling in these stromal cells transiently hinders the early phase of thymic reconstitution following myeloablative conditioning and hematopoietic stem cell transplantation. Hence, inhibition of TGF-beta signaling decelerates the process of age-related thymic involution and may hasten the reconstitution of regular thymopoiesis following hematopoietic stem cell transplantation.
Advisors:Holländer, Georg A.
Committee Members:Rolink, Antonius G. and Palmer, Ed
Faculties and Departments:03 Faculty of Medicine > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Pädiatrische Immunologie (Holländer)
Item Type:Thesis
Thesis no:9129
Bibsysno:Link to catalogue
Number of Pages:145 S.
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:41
Deposited On:01 Oct 2010 07:09

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