Aging is associated with increased regulatory T‐cell function

Aging Cell

Sanjay K. Garg¹  Colin Delaney¹  Tomomi Toubai²  Amiya Ghosh¹  Pavan Reddy²  Ruma Banerjee³ 

[1] Division of Geriatrics and Palliative Medicine, Ann Arbor, USA;Division of Hematology and Oncology, Department of Internal Medicine, Ann Arbor, USA;Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, USA

关键词: aging;    epigenetics;    methylation;    redox;    regulatory T cell;   

DOI  :  10.1111/acel.12191

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

CC BY   
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.