Aging is associated with increased regulatory T-cell function
| Autor: | Amiya K. Ghosh, Raymond Yung, Tomomi Toubai, Sanjay K. Garg, Ruma Banerjee, Colin Delaney, Pavan Reddy |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
Epigenomics Male regulatory T cell Aging Regulatory T cell chemical and pharmacologic phenomena Biology CD8-Positive T-Lymphocytes Methylation T-Lymphocytes Regulatory 03 medical and health sciences Mice 0302 clinical medicine Immune system Extracellular medicine Animals IL-2 receptor 030304 developmental biology Cell Proliferation CD86 0303 health sciences epigenetics Cell growth Effector FOXP3 hemic and immune systems Forkhead Transcription Factors Cell Biology Original Articles Mice Inbred C57BL medicine.anatomical_structure redox Immunology Oxidation-Reduction 030217 neurology & neurosurgery |
| Zdroj: | Aging Cell |
| ISSN: | 1474-9726 1474-9718 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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