[HTML][HTML] Ghrelin promotes thymopoiesis during aging

VD Dixit, H Yang, Y Sun, AT Weeraratna… - The Journal of …, 2007 - Am Soc Clin Investig
VD Dixit, H Yang, Y Sun, AT Weeraratna, YH Youm, RG Smith, DD Taub
The Journal of clinical investigation, 2007Am Soc Clin Investig
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 …
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 LinSca1+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.
The Journal of Clinical Investigation