title: Loss of Pten Disrupts the Thymic Epithelium and Alters Thymic Function.
abstract: The thymus is the site of T cell development and selection. In addition to lymphocytes, the thymus is composed of several types of stromal cells that are exquisitely organized to create the appropriate environment and microenvironment to support the development and selection of maturing T cells. Thymic epithelial cells (TECs) are one of the more important cell types in the thymic stroma, and they play a critical role in selecting functional T cell clones and supporting their development. In this study, we used a mouse genetics approach to investigate the consequences of deleting the Pten tumor suppressor gene in the TEC compartment of the developing thymus. We found that PTEN deficiency in TECs results in a smaller thymus with significantly disordered architecture and histology. Accordingly, loss of PTEN function also results in decreased T cells with a shift in the distribution of T cell subtypes towards CD8+ T cells. These experiments demonstrate that PTEN is critically required for the development of a functional thymic epithelium in mice. This work may help better understand the effects that certain medical conditions or clinical interventions have upon the thymus and immune function.
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, United States of America.|Department of Genetics, Stanford University, Stanford, CA, United States of America.
authors.forename: Phillip M
authors.initials: PM
authors.lastname: Garfin
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, United States of America.|Department of Genetics, Stanford University, Stanford, CA, United States of America.
authors.forename: Thuyen
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, United States of America.|Department of Genetics, Stanford University, Stanford, CA, United States of America.
authors.forename: Julien
authors.initials: J
authors.lastname: Sage
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D017353:Gene Deletion; D051379:Mice; D009929:Organ Size; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000033:anatomy & histology / Q000166:cytology* / Q000276:immunology / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D016160:Retinoblastoma Protein; D051059:PTEN Phosphohydrolase