Potentiation of Th17 cytokines in aging process contributes to the development of colitis

Abstract

SummaryTh17 cells, which produce IL-17 and IL-22, promote autoimmunity in mice and have been implicated in the pathogenesis of autoimmune/inflammatory diseases in humans. However, the Th17 immune response in the aging process is still not clear. In the present study, we found that the induction of IL-17-produing CD4 + T cells was significantly increased in aged individuals compared with young healthy ones. The mRNA expression of IL-17, IL-17F, IL-22, and RORC2 was also significantly increased in aged people. Similar to humans, Th17 cells as well as mRNAs encoding IL-17, IL-22 and RORγt were dramatically elevated in naïve T cells from aged mouse compared to young ones. In addition, CD44 positive IL-17-producing CD4 + T cells were significantly higher in aged mice, suggesting that memory T cells are an important source of IL-17 production. Furthermore, the percentage of IL-17-produing CD4 + T cells generated in co-culture with dendritic cells from either aged or young mice did not show significant differences, suggesting that dendritic cells do not play a primary role in the elevation of Th17 cytokines in aged mouse cells. Importantly, transfer of CD4 + CD45Rb hi cells from aged mice induced more severe colitis in RAG −/− mice compared to cells from young mice, Taken together, these results suggest that Th17 immune responses are elevated in aging humans and mice and may contribute to the increased development of inflammatory disorders in the elderly.

A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice

“…Indeed, augmented Th17 activity is implicated in autoimmune and inflammatory diseases, including age-associated colitis in both mice and humans. 50 While understanding the full role of ABCs in immunosenescence awaits further investigation, our findings identify them as a phenotypically and functionally unique B-cell subset that occupies an increasing proportion of the primary B-cell niche with age.…”

Aged regulatory T cells protect from autoimmune inflammation despite reduced STAT3 activation and decreased constraint of IL‐17 producing T cells

“…Differences in gut flora, which is well known to alter immunity (Ouyang et al, 2011), or other factors to be determined could also be responsible. These differences demonstrate that a detailed understanding of immune cell subsets, in addition to other variables, requires significant additional attention in studies of aging and immunity.…”

Extrathymic induction of Foxp3+ regulatory T cells declines with age in a T‐cell intrinsic manner

“…Saturating amounts of TGF-β were unable to reverse this reduction in old T cells (data not shown). As TGF-β-dependent Th17 induction is enhanced in aged T cells [21,22], we presumed that TGF-β signaling is intact in aged T cells. Most importantly, we cocultured naïve Tconv cells from young mice at different ratio with naïve Tconv cells from old mice and found no inhibitory effects on the conversion of young naïve Tconv cells (Fig.…”