Ghrelin promotes thymopoiesis during aging
Vishwa Deep Dixit, … , Roy G. Smith, Dennis D. Taub
Vishwa Deep Dixit, … , Roy G. Smith, Dennis D. Taub
Published October 1, 2007
Citation Information: J Clin Invest. 2007;117(10):2778-2790. https://doi.org/10.1172/JCI30248.
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Research Article Immunology

Ghrelin promotes thymopoiesis during aging

Abstract

The decline in adaptive immunity, T lymphocyte output, and the contraction of the TCR repertoire with age is largely attributable to thymic involution. The loss of thymic function with age may be due to diminished numbers of progenitors and the loss of critical cytokines and hormones from the thymic microenvironment. We have previously demonstrated that the orexigenic hormone ghrelin is expressed by immune cells and regulates T cell activation and inflammation. Here we report that ghrelin and ghrelin receptor expression within the thymus diminished with progressive aging. Infusion of ghrelin into 14-month-old mice significantly improved the age-associated changes in thymic architecture and thymocyte numbers, increasing recent thymic emigrants and improving TCR diversity of peripheral T cell subsets. Ghrelin-induced thymopoiesis during aging was associated with enhanced early thymocyte progenitors and bone marrow–derived Lin–Sca1+cKit+ cells, while ghrelin- and growth hormone secretagogue receptor–deficient (GHS-R–deficient) mice displayed enhanced age-associated thymic involution. Leptin also enhanced thymopoiesis in aged but not young mice. Our findings demonstrate what we believe to be a novel role for ghrelin and its receptor in thymic biology and suggest a possible therapeutic benefit of harnessing this pathway in the reconstitution of thymic function in immunocompromised subjects.

Authors

Vishwa Deep Dixit, Hyunwon Yang, Yuxiang Sun, Ashani T. Weeraratna, Yun-Hee Youm, Roy G. Smith, Dennis D. Taub

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Figure 1

The GHS-R expression in thymus.

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The GHS-R expression in thymus. (A) The ghrelin binding sites exist larg...
(A) The ghrelin binding sites exist largely in the medullary area of the thymus. Frozen thymic sections were labeled with FAM-conjugated ghrelin (FAM-Grln) and stained with medullary epithelial cell marker, Alexa Fluor 594–conjugated anti–Ker5 (K5) antibody and counter-stained with DAPI for nuclei. Ghrelin binding sites (green) are largely segregated from Ker5-expressing cells in the cortex (C; red), as shown by lack of a yellow staining pattern, which would suggest colocalization (line depicts the CMJ in the thymus). M, medulla. (B) Similar to FAM-ghrelin binding, the GHS-R antibody–positive cells displayed only modest colocalization with Ker5+ medullary TECs. (C) GHS-R (red) displayed little to no colocalization with cortical Ker8+ and medullary UEA-1+ TECs. However, a minor subset of Ker8+ cells in the medulla displayed GHS-R immunopositivity. (D) Thymus and sorted SP, DP, and DN thymocytes express GHS-R mRNA. DP cells expressed 2-fold higher GHS-R than did SP and DN cells, with levels comparable to those of the pituitary. Numbers above the blot indicate the ratio of GHS-R to GAPDH expression. –ve C, negative control. Original magnification, ×10.