Scientific Publications
Age-associated modifications of intestinal permeability and innate immunity in the human small intestine
Clinical Science, 129, 515-527
The effect of ageing on the physical and immunoregulatory properties of the human intestinal epithelial barrier is largely unknown. We assessed age-associated changes of levels of inflammatory cytokines, barrier integrity, and epithelial innate immunity to microbial challenge in the small intestine of healthy individuals. Ileal biopsies from adult (20-40 years old), ageing (67-77y) and young (7-12y) individuals were used. mRNA level of cytokines (IL-6, IFNƒ×TNF-ƒÑ and IL-1ƒÒ) was assessed by quantitative qRT-PCR. Epithelial integrity was evaluated by monitoring intestinal permeability and mRNA expression of tight junction proteins (zonula occludens 1, occludin and claudin 2) while a polarized in vitro organ culture was used to determine epithelial innate immunity to microbial stimuli. Increased expression of IL-6, but not IFNg, TNF-a and IL-1b was observed in the aged group. Also, biopsies from aged group displayed reduced transepithelial electric resistance associated to increased expression of claudin-2; instead, zonula occludens-1, and occludin did not vary with age. Barrier integrity was restored in vitro and in ex-vivo cultures by addition of anti-IL-6 antibody. Finally, we observed that epithelial immunity in ageing varied according to the antigen. IL-8 production in response to flagellin declined with age although the expression of TLR5 on epithelial cells remained unchanged; in contrast, production of TNF-a in response to a more complex microbial antigen (probiotics) did not decline with age. These data show that ageing affects properties of the human intestinal epithelial barrier that might have direct bearing on age-associated disturbances both locally and systemically.
Clinical Science, 129, 515-527
View Publication
