Intestinal T cells in aging: implications for gut barrier integrity and inflammaging

Area of Science:

• Immunology
• Gastroenterology
• Aging Research

Background:

• Aging progressively degrades intestinal barrier integrity, increasing permeability and promoting chronic inflammation (inflammaging).
• While epithelial and microbial factors are studied, the role of intestinal T cells in age-related barrier decline is underappreciated.
• The gut hosts a vast T-cell population crucial for epithelial homeostasis via cytokine signaling.

Purpose of the Study:

• To review and synthesize evidence connecting age-related changes in intestinal T cells to epithelial barrier dysfunction.
• To examine specific T-cell subsets and their altered functions during aging.
• To explore how T-cell senescence and exhaustion exacerbate barrier defects and systemic inflammation.

Main Methods:

• Literature review synthesizing current evidence on intestinal T cells and aging.
• Focus on key T-cell subsets: Th1, Th17, Th22, Tregs, γδ T cells, MAIT cells, IELs.
• Analysis of age-associated shifts in T-cell cytokine profiles and functional phenotypes.

Main Results:

• Aging alters the composition and function of intestinal T cells, disrupting barrier homeostasis.
• Shifts in T-cell cytokine profiles contribute to an imbalance between barrier maintenance, repair, and inflammation.
• Senescent and exhausted T cells exacerbate epithelial injury, microbial translocation, and systemic immune activation.

Conclusions:

• Intestinal T cells are critical regulators of barrier integrity whose age-related dysfunction significantly contributes to barrier decline.
• Understanding T-cell roles in aging is vital for developing strategies to combat inflammaging and associated diseases.
• Insights from accelerated aging models inform T-cell-driven barrier decline in the general aging population.