Ghrelin promotes thymopoiesis during aging

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2778-2790
Number of pages13
JournalJournal of Clinical Investigation
Volume117
Issue number10
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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