title: Thymic epithelial cell expansion through matricellular protein CYR61 boosts progenitor homing and T-cell output.
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.
authors.affiliation: Department of Pathology and Immunology, University of Geneva, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Genève 4, Switzerland.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Emre
authors.forename: Magali
authors.initials: M
authors.lastname: Irla
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dunand-Sauthier
authors.forename: Romain
authors.initials: R
authors.lastname: Ballet
authors.forename: Mehdi
authors.initials: M
authors.lastname: Meguenani
authors.forename: Stephane
authors.initials: S
authors.lastname: Jemelin
authors.forename: Christian
authors.initials: C
authors.lastname: Vesin
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
authors.forename: Beat A
authors.initials: BA
authors.lastname: Imhof
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011485:Protein Binding; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism
chemical_list: D055515:Cysteine-Rich Protein 61; D039503:Integrin alpha6; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1