Aging correlates with reduction in regulatory-type cytokines and T cells in the gut mucosa

• Published in: Immunobiology (1979) 2011-10, Vol.216 (10), p.1085-1093
• Main Authors: Santiago, Andrezza F, Alves, Andréa C, Oliveira, Rafael P, Fernandes, Raphaela M, Paula-Silva, Josiely, Assis, Frankcineia A, Carvalho, Cláudia R, Weiner, Howard L, Faria, Ana Maria C
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Aging; Aging - immunology; Allergy and Immunology; Animals; Antigen-Presenting Cells - immunology; Cytokines - biosynthesis; Cytokines - immunology; Dendritic cells; Female; IL-10; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intra-epithelial lymphocytes; Mice; Mice, Inbred BALB C; Mice, Transgenic; Oral tolerance; Phenotype; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; TGF-β
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2011.05.007

Abstract Aging is reported to be associated with decline in oral tolerance induction, which is initiated at the intestinal mucosal surface. Herein, we examined the effect of aging in T cells and cytokines at the intestinal mucosa that might be involved in oral tolerance induction. Frequencies of regulatory-type IEL subsets such as TCRγδ+ and TCRαβ+ CD8αα+ were lower in aged mice. Mucosal CD4+ CD25+ Foxp3+ and CD4+ LAP+ T cells increased with aging but activated CD44+ CD4+ mucosal T cells also augmented. Production of TGF-β and IL-10 in the small intestine of old mice was reduced. Moreover, the ability of mucosal dendritic cells of aged mice to stimulate TGF-β secretion and differentiation of CD4+ LAP+ T cells in co-culture studies also declined with aging. Reduction in these regulatory-type cytokines and T cells may help to explain the decline in susceptibility to oral induction during aging. However, not all mucosal regulatory elements were altered by aging and CD4+ CD25+ Foxp3+ T cells were especially resistant to changes. Persistence of some mechanisms of regulation may play a critical role in maintaining mucosal homeostasis during aging.