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Defective Central Immune Tolerance Induced by High-Dose D-Galactose Resembles Aging

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Abstract

D-Galactose (D-Gal) promotes accumulation of reactive oxygen species and formation of advanced glycation end-products, ultimately resulting in oxidative stress. D-Gal has been widely used to induce accelerated aging in anti-aging medical research. Although thymic epithelial cells are particularly sensitive to oxidative stress, there are few reports on the thymus changes accompanying D-Gal-induced aging in mice. To study the effect of D-Gal on rodent thymus, we investigated the degree of thymus atrophy and changes in the atrophy relative index in C57BL/6J mice following subcutaneous injection of D-Gal at different doses (200, 500, 1000 mg/kg per day) for 60 days. Compared with the vehicle-treated (0.9% saline) and young controls, D-Gal at doses of 500 and 1000 mg/kg per day led to a significant thymic atrophy; the latter dose caused atrophy similar to that observed in naturally aged (18-20-month-old) mice. Mice treated with high-dose D-Gal exhibited greater immunosenescence, defective central immune tolerance, increased levels of activated splenic immune cell, and chronic low-grade inflammation, i.e., outcomes similar to those observed in natural aging in mice. Taken together, our results indicate that mice treated with high-dose D-Gal may be a valid model for studying induced thymic atrophy and effects of aging on the immune system.

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Abbreviations

D-Gal:

D-galactose

MDA:

malondialdehyde

NS:

normal saline

ROS:

reactive oxygen species

RTE:

recent thymic emigrant

SAMP:

senescence-accelerated mouse prone (model)

SOD:

superoxide dismutase

TEC:

thymic epithelial cell

TRA:

tissue-restricted antigen

tTreg:

thymic regulatory T cell

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Acknowledgements

The authors wish to thank the International Science Editing (http://www.international-scienceediting.com) for their assistance in the preparation of this manuscript.

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Authors and Affiliations

  1. Research Center, Shengjing Hospital of China Medical University, Economic Development Zone, 117000, Benxi, China

    H. M. Du, Y. J. Wang, X. Liu & X. K. Zhu

  2. Department of Oncology, Shengjing Hospital of China Medical University, 110022, Shenyang, China

    H. M. Du & S. L. Wang

  3. Department of Blood Transfusion, Shengjing Hospital of China Medical University, 110022, Shenyang, China

    S. M. Wu & Z. Yuan

Authors
  1. H. M. Du
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  2. Y. J. Wang
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  3. X. Liu
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  4. S. L. Wang
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  5. S. M. Wu
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Correspondence to X. K. Zhu.

Additional information

Published in Russian in Biokhimiya, 2019, Vol. 84, No. 6, pp. 795-807.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM18-334, April 29, 2019.

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Du, H.M., Wang, Y.J., Liu, X. et al. Defective Central Immune Tolerance Induced by High-Dose D-Galactose Resembles Aging. Biochemistry Moscow 84, 617–626 (2019). https://doi.org/10.1134/S000629791906004X

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  • DOI: https://doi.org/10.1134/S000629791906004X

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