TY - JOUR
T1 - Tumor-induced thymic atrophy
T2 - Alteration in interferons and Jak/Stats signaling pathways
AU - Carrio, Roberto
AU - Torroella-Kouri, Marta
AU - Iragavarapu-Charyulu, Vijaya
AU - Lopez, Diana M.
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - Interferons
KW - Jak/Stat pathways
KW - Thymus atrophy
KW - Tumor-bearing mice
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U2 - 10.3892/ijo.2010.870
DO - 10.3892/ijo.2010.870
M3 - Article
C2 - 21165556
AN - SCOPUS:78651230633
VL - 38
SP - 547
EP - 553
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 2
ER -