Thymic Epithelial Cell Support of Thymopoiesis Does Not Require
| Autor: | Kenneth I. Weinberg, Ron T. McElmurry, Georg A. Holländer, Yan Xing, Michelle J. Smith, Jakub Tolar, Heather E. Stefanski, Sarah L. Parker, Dullei Min, Christine A. Goetz, Bruce R. Blazar |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Premature aging medicine.medical_specialty Aging Diet therapy T cell T-Lymphocytes Immunology Thymus Gland Biology urologic and male genital diseases Article 03 medical and health sciences Mice Internal medicine medicine Immunology and Allergy Animals Vitamin D Klotho Klotho Proteins Cells Cultured Glucuronidase Mice Knockout Thymic involution Transplantation Thymocytes Aging Premature Epithelial Cells Adoptive Transfer female genital diseases and pregnancy complications Fibroblast Growth Factors Mice Inbred C57BL Thymocyte 030104 developmental biology medicine.anatomical_structure Endocrinology CD8 Diet Therapy |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 201(11) |
| ISSN: | 1550-6606 |
| Popis: | Age-related thymic involution is characterized by a decrease in thymic epithelial cell (TEC) number and function parallel to a disruption in their spatial organization, resulting in defective thymocyte development and proliferation as well as peripheral T cell dysfunction. Deficiency of Klotho, an antiaging gene and modifier of fibroblast growth factor signaling, causes premature aging. To investigate the role of Klotho in accelerated age-dependent thymic involution, we conducted a comprehensive analysis of thymopoiesis and peripheral T cell homeostasis using Klotho-deficient (Kl/Kl) mice. At 8 wk of age, Kl/Kl mice displayed a severe reduction in the number of thymocytes (10–100-fold reduction), especially CD4 and CD8 double-positive cells, and a reduction of both cortical and medullary TECs. To address a cell-autonomous role for Klotho in TEC biology, we implanted neonatal thymi from Klotho-deficient and -sufficient mice into athymic hosts. Kl/Kl thymus grafts supported thymopoiesis equivalently to Klotho-sufficient thymus transplants, indicating that Klotho is not intrinsically essential for TEC support of thymopoiesis. Moreover, lethally irradiated hosts given Kl/Kl or wild-type bone marrow had normal thymocyte development and comparably reconstituted T cells, indicating that Klotho is not inherently essential for peripheral T cell reconstitution. Because Kl/Kl mice have higher levels of serum phosphorus, calcium, and vitamin D, we evaluated thymus function in Kl/Kl mice fed with a vitamin D–deprived diet. We observed that a vitamin D–deprived diet abrogated thymic involution and T cell lymphopenia in 8-wk-old Kl/Kl mice. Taken together, our data suggest that Klotho deficiency causes thymic involution via systemic effects that include high active vitamin D levels. |
| Databáze: | OpenAIRE |
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