A regulatory role for TGF-beta signaling in the establishment and function of the thymic medulla

Hauri-Hohl, M. and Zuklys, S. and Holländer, G. A. and Ziegler, S. F.. (2014) A regulatory role for TGF-beta signaling in the establishment and function of the thymic medulla. Nature immunology, 15 (6). pp. 554-561.

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Medullary thymic epithelial cells (mTECs) are critical in establishing and maintaining the appropriate microenvironment for negative selection and maturation of immunocompetent T cells with a self-tolerant T cell antigen receptor repertoire. Cues that direct proliferation and maturation of mTECs are provided by members of the tumor necrosis factor (TNF) superfamily expressed on developing thymocytes. Here we demonstrate a negative role of the morphogen TGF-beta in tempering these signals under physiological conditions, limiting both growth and function of the thymic medulla. Eliminating TGF-beta signaling specifically in TECs or by pharmacological means increased the size of the mTEC compartment, enhanced negative selection and functional maturation of medullary thymocytes as well as the production of regulatory T cells, thus reducing the autoreactive potential of peripheral T cells.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Children's Hospital > Pediatric Immunology (Holländer)
UniBasel Contributors:Holländer, Georg
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature America
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Jun 2020 11:16
Deposited On:01 Jun 2020 11:16

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