title: Tumor-induced thymic atrophy: alteration in interferons and Jak/Stats signaling pathways.
abstract: The thymus is the major site of T cell differentiation and a key organ of the immune system. Thym atrophy has been observed in several model systems including aging, and tumor development. Previous results from our laboratory have reported that the thymic atrophy seen in mammary tumor bearers is associated with a severe depletion of CD4+CD8+ double positive immature cells and changes in the levels of cytokines expressed in the thymus microenvironment. Cytokines regulate numerous aspects of hematopoiesis via activation of the Jak/Stat pathways. In the present study we have used our mammary tumor model to investigate whether changes in the levels of cytokines in the thymus could affect the normal expression of the aforementioned pathways. RNA and protein analysis revealed an overexpression of the different members of interferons, a downregulation of most of the Jak/Stat pathways, and an increased expression of several suppressors of cytokine signaling (SOSC) in the thymuses of tumor bearers. Together, our data suggest that the impaired Jak/Stat signaling pathways observed in the whole thymus of tumor-bearing mice could be contributing to the abnormal T cell development and apoptosis observed during the tumor-induced thymic atrophy.
authors.affiliation: Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Carrio
authors.forename: Marta
authors.initials: M
authors.lastname: Torroella-Kouri
authors.forename: Vijaya
authors.initials: V
authors.lastname: Iragavarapu-Charyulu
authors.forename: Diana M
authors.initials: DM
authors.lastname: Lopez
mesh_terms: D000818:Animals; D001284:Atrophy; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007372:Interferons / Q000378:metabolism; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology*; D013953:Thymus Neoplasms / Q000276:immunology / Q000473:pathology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D007372:Interferons; D053613:Janus Kinase 1