Thymic Epithelial Cell Support of Thymopoiesis Does Not Require Klotho .

Autor:	Xing Y; Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455., Smith MJ; Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455.; Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455., Goetz CA; Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455.; Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455., McElmurry RT; Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455., Parker SL; Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455., Min D; Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford Medicine, Stanford University, Palo Alto, CA 94304., Hollander GA; Department of Biomedicine, University of Basel, 4056 Basel, Switzerland; and.; Department of Paediatrics, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom., Weinberg KI; Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford Medicine, Stanford University, Palo Alto, CA 94304., Tolar J; Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455., Stefanski HE; Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455., Blazar BR; Division of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455; blaza001@umn.edu.; Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Dec 01; Vol. 201 (11), pp. 3320-3328. Date of Electronic Publication: 2018 Oct 29.
DOI:	10.4049/jimmunol.1800670
Abstrakt:	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. (Copyright © 2018 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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