Published online before print April 1, 2009

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(Journal of Leukocyte Biology. 2009;85:928-938.)
© 2009 by Society for Leukocyte Biology

Axin expression in thymic stromal cells contributes to an age-related increase in thymic adiposity and is associated with reduced thymopoiesis independently of ghrelin signaling

Hyunwon Yang^*, Yun-Hee Youm^*, Yuxiang Sun, Jong-Seop Rim, Craig J. Galbán, Bolormaa Vandanmagsar^* and Vishwa Deep Dixit^*,1

^* Laboratory of Neuroendocrine-Immunology,
Division of Experimental Obesity, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA;
Huffington Center on Aging, Baylor College of Medicine, Houston, Texas, USA; and
Radiology Department, University of Michigan, Ann Arbor, Michigan, USA

¹ Correspondence: Laboratory of Neuroendocrine-Immunology, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Rd., Baton Rouge, LA 70808, USA. E-mail: Vishwa.dixit{at}pbrc.edu

ABSTRACT

The adipocytes are the predominant cell types that constitute the bulk of the thymic microenvironment by the fifth decade of life in healthy humans. An age-related increase in thymic adiposity is associated with reduced thymopoiesis and compromised immune surveillance in the elderly. However, the mechanisms regulating the generation of intrathymic adipocytes during aging remain to be elucidated. Here, we report that the CD45^– thymic stromal cells (TSCs) are amenable to adipogenesis. We identified that the Wnt inhibitor axin is expressed in the lymphoid as well as stromal cells of the thymus with increased expression in CD45^– TSCs of older mice. Knockdown of axin by RNA interference in CD45^– primary TSCs led to a marked reduction in adipogenesis with significantly lower expression of adipogenic transcripts peroxisome proliferator-activated receptor 2 (PPAR), adipocyte fatty acid-binding protein (aP2), and perilipin. Age-related elevated axin expression was increased specifically in thymic fibroblasts and medullary thymic epithelial cells (TECs) but not in the cortical TEC or CD45⁺ cells. Consistent with a role of axin in promoting thymic adipogenesis, axin expression was also colocalized with lipid-expressing adipogenic cells in aging thymus. The prolongevity intervention, caloric restriction (CR), prevented the age-related increase in axin and the adipogenic cell in the thymus together with increase in thymic output. We have recently demonstrated that CR induces ghrelin, which can partially reverse thymic involution. Here, we show that axin expression is not affected by ablation of ghrelin receptors in aging mice, suggesting a ghrelin-independent mechanism for regulation of axin. Our data are consistent with the hypothesis that blocking the specific proadipogenic signals in the thymus may complement the present approaches to rejuvenate thymic function during aging.

Key Words: aging • Wnt • adipogenesis • GH • adipocyte • dietary restriction • obesity

This article has been cited by other articles:

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