Thymic epithelial cell expansion through matricellular protein CYR61 boosts progenitor homing and T-cell output

Yalin Emre (), Magali Irla, Isabelle Dunand-Sauthier, Romain Ballet, Mehdi Meguenani, Stephane Jemelin, Christian Vesin, Walter Reith and Beat A. Imhof
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Yalin Emre: University of Geneva, Centre Médical Universitaire
Magali Irla: University of Geneva, Centre Médical Universitaire
Isabelle Dunand-Sauthier: University of Geneva, Centre Médical Universitaire
Romain Ballet: University of Geneva, Centre Médical Universitaire
Mehdi Meguenani: University of Geneva, Centre Médical Universitaire
Stephane Jemelin: University of Geneva, Centre Médical Universitaire
Christian Vesin: University of Geneva, Centre Médical Universitaire
Walter Reith: University of Geneva, Centre Médical Universitaire
Beat A. Imhof: University of Geneva, Centre Médical Universitaire

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: Abstract Thymic epithelial cells (TEC) are heterogeneous stromal cells that generate microenvironments required for the formation of T cells within the thymus. Defects in TEC lead to immunodeficiency or autoimmunity. Here we identify TEC as the major source of cysteine-rich protein 61 (CYR61), a matricellular protein implicated in cell proliferation and migration. Binding of CYR61 to LFA-1, ICAM-1 and integrin α6 supports the adhesion of TEC and thymocytes as well as their interaction. Treatment of thymic lobes with recombinant CYR61 expands the stromal compartment by inducing the proliferation of TEC and activates Akt signalling. Engraftment of CYR61-overexpressing thymic lobes into athymic nude mice drastically boosts the yield of thymic output via expansion of TEC. This increases the space for the recruitment of circulating hematopoietic progenitors and the development of T cells. Our discovery paves the way for therapeutic interventions designed to restore thymus stroma and T-cell generation.

Date: 2013
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DOI: 10.1038/ncomms3842

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