Ghrelin promotes thymopoiesis during aging
Vishwa Deep Dixit, Hyunwon Yang, Yuxiang Sun, Ashani T. Weeraratna, Yun-Hee Youm, Roy G. Smith, Dennis D. Taub
Vishwa Deep Dixit, Hyunwon Yang, Yuxiang Sun, Ashani T. Weeraratna, Yun-Hee Youm, Roy G. Smith, Dennis D. Taub
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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 8

Ghrelin and GHS-R–deficient mice demonstrate accelerated age-associated thymic involution.

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Ghrelin and GHS-R–deficient mice demonstrate accelerated age-associated ...
(A) Thymocyte counts in ghrelin–/– and GHS-R–/– mice did not differ at 2 months of age but were significantly reduced at 24 months of age. (B) The histological examination of thymus from 24-month-old ghrelin–/– mice revealed a greater loss of CMJs, reduced cellularity, and an increased number of adipocytes in the thymus. Original magnification, ×10 (upper and lower panels); ×20 (middle panels). A similar reduction in cellularity and enhanced thymic involution from age-matched littermates was observed in GHS-R–/– mice. (C) GHS-R–/– mice displayed an increase in cortical adipocyte infiltration with no significant difference in intrathymic GH expression (arrowheads). Original magnification, ×40. (D) GHS-R–deficient mice did not show significant change in serum IGF-1 levels. (E) Ghrelin promoted thymopoiesis in 12-month-old mice via GHS-R–specific pathway. The 2-week-long ghrelin infusions increased the thymocyte number in WT mice but not in GHSR–/– mice.