SEARCH:   Advanced

Blood, 29 October 2009, Vol. 114, No. 18, pp. 3803-3812. Prepublished online as a Blood First Edition Paper on August 31, 2009; DOI 10.1182/blood-2009-03-213595. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2009-03-213595v1 114/18/3803    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Yang, H. Articles by Dixit, V. D. PubMed PubMed Citation Articles by Yang, H. Articles by Dixit, V. D. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Obesity accelerates thymic aging Hyunwon Yang1, Yun-Hee Youm1, Bolormaa Vandanmagsar1, Jennifer Rood2, K. Ganesh Kumar3, Andrew A. Butler3, and Vishwa Deep Dixit1 1 Laboratory of Neuroendocrine-Immunology, 2 Clinical Chemistry Core, and 3 Neuropeptide Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge As the expanding obese population grows older, their successful immunologic aging will be critical to enhancing the health span. Obesity increases risk of infections and cancer, suggesting adverse effects on immune surveillance. Here, we report that obesity compromises the mechanisms regulating T-cell generation by inducing premature thymic involution. Diet-induced obesity reduced thymocyte counts and significantly increased apoptosis of developing T-cell populations. Obesity accelerated the age-related reduction of T-cell receptor (TCR) excision circle bearing peripheral lymphocytes, an index of recently generated T cells from thymus. Consistent with reduced thymopoiesis, dietary obesity led to reduction in peripheral naive T cells with increased frequency of effector-memory cells. Defects in thymopoiesis in obese mice were related with decrease in the lymphoid-primed multipotent progenitor (Lin–Sca1+Kit+ Flt3+) as well as common lymphoid progenitor (Lin–Sca1+CD117loCD127+) pools. The TCR spectratyping analysis showed that obesity compromised V-β TCR repertoire diversity. Furthermore, the obesity induced by melanocortin 4 receptor deficiency also constricted the T-cell repertoire diversity, recapitulating the thymic defects observed with diet-induced obesity. In middle-aged humans, progressive adiposity with or without type 2 diabetes also compromised thymic output. Collectively, these findings establish that obesity constricts T-cell diversity by accelerating age-related thymic involution. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020