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Regeneration of dendritic cells in aged mice

Cellular & Molecular Immunology volume 7, pages 108–115 (2010)Cite this article

Abstract

Age-related thymic involution causes a decreased output of thymocytes from the thymus, thereby resulting in impairment of T cell-mediated immunity. While alterations in the T cell and non-haematopoietic stromal compartments have been described, the effects of thymic involution on thymic dendritic cells (DC) are not clearly known. Thymic DC play an essential role in shaping T cell-mediated immune responses by deleting self-reactive thymocytes to establish central tolerance and by inducing regulatory T-cell (Treg) development. It is therefore important to assess the prevalence of and alterations to thymic DC with age, as this may impact on their function. We assessed the numbers and proportions of the three distinct subsets of thymic DC in ageing mice, and showed that these subsets are differentially regulated. This is expected as thymic DC subsets have different origins of development. We further assessed the responses of thymic DC in a regenerative environment, such as that induced by sex-steroid ablation (SSA), and clearly showed that, consistent with global thymus regrowth, all three DC populations increased in numbers and regained their relative proportions to thymocytes after an initial lag period. These findings are important for the clinical translation of thymic regenerative approaches, and indicate that SSA facilitates the maintenance of critical processes such as negative selection and Treg induction through promoting thymic DC regeneration.

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Acknowledgements

We thank J. Homann for performing the castration operations and animal husbandry. L. Wu, K. Shortman and S. van Dommelen are supported by a grant from the Australian Stem Cell Centre. L. Wu and K. Shortman are supported by fellowships and grants from the Australian National Health and Medical Research Council.

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Author notes

  1. Alexandra Rizzitelli

    Present address: Current address: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic., Australia

Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia

    Serani LH van Dommelen, Alexandra Rizzitelli, Ken Shortman & Li Wu

  2. Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Vic., Australia

    Ann Chidgey & Richard Boyd

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  1. Serani LH van Dommelen
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Correspondence to Li Wu.

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van Dommelen, S., Rizzitelli, A., Chidgey, A. et al. Regeneration of dendritic cells in aged mice. Cell Mol Immunol 7, 108–115 (2010). https://doi.org/10.1038/cmi.2009.114

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