These authors contributed equally to this work.
Aging is associated with increased regulatory T-cell function
Article first published online: 25 FEB 2014
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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How to Cite
Garg, S. K., Delaney, C., Toubai, T., Ghosh, A., Reddy, P., Banerjee, R. and Yung, R. (2014), Aging is associated with increased regulatory T-cell function. Aging Cell. doi: 10.1111/acel.12191
- Article first published online: 25 FEB 2014
- Accepted manuscript online: 10 DEC 2013 08:36AM EST
- Manuscript Accepted: 29 NOV 2013
- NIH. Grant Numbers: AG020628, AG028268, HL58984
- University of Michigan Claude D. Pepper Older American Independence Center. Grant Number: AG024824
- Nathan Shock Center for the Basic Biology of Aging. Grant Numbers: AG013283, AG013283
- Center for the Study of Lifestage Exposures and Adult Disease. Grant Number: ES017885
- Caner Center Microarray Core
- Michigan Diabetes and Research Training Center Animal Phenotyping Core
- Geriatrics Research, Education and Clinical Care Center
- VA Ann Arbor Healthcare System
- regulatory T cell
Regulatory T-cell (Treg, CD4+CD25+) dysfunction is suspected to play a key role in immune senescence and contributes to increased susceptibility to diseases with age by suppressing T-cell responses. FoxP3 is a master regulator of Treg function, and its expression is under control of several epigenetically labile promoters and enhancers. Demethylation of CpG sites within these regions is associated with increased FoxP3 expression and development of a suppressive phenotype. We examined differences in FoxP3 expression between young (3–4 months) and aged (18–20 months) C57BL/6 mice. DNA from CD4+ T cells is hypomethylated in aged mice, which also exhibit increased Treg numbers and FoxP3 expression. Additionally, Treg from aged mice also have greater ability to suppress effector T-cell (Teff) proliferation in vitro than Tregs from young mice. Tregs from aged mice exhibit greater redox remodeling–mediated suppression of Teff proliferation during coculture with DCs by decreasing extracellular cysteine availability to a greater extent than Tregs from young mice, creating an adverse environment for Teff proliferation. Tregs from aged mice produce higher IL-10 levels and suppress CD86 expression on DCs more strongly than Tregs from young mice, suggesting decreased T-cell activity. Taken together, these results reveal a potential mechanism of higher Treg-mediated activity that may contribute to increased immune suppression with age.