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

Abstract

Aging is accompanied by a progressive decline in intestinal barrier integrity, resulting in increased permeability to luminal microbes and microbial products and contributing to chronic low-grade inflammation ("inflammaging"). While epithelial and microbial changes have been extensively studied, the role of intestinal T cells as active regulators of barrier homeostasis during aging remains underappreciated. The gut harbors the largest population of T cells in the body, including diverse conventional and unconventional subsets that directly shape epithelial differentiation, mucus production, antimicrobial defense, and tight junction organization through cytokine-mediated signaling. In this review, we synthesize current evidence linking age-related alterations in intestinal T-cell composition and function to epithelial barrier decline. We focus on key T-cell subsets including Th1, Th17, Th22, regulatory T cells, γδ T cells, mucosal-associated invariant T (MAIT) cells, and intraepithelial lymphocytes, and discuss how aging-associated shifts in their cytokine profiles may disrupt the balance between barrier maintenance, repair, and inflammation. We further examine how T-cell dysfunctions characteristic of aging, including senescent-like and exhausted phenotypes, may exacerbate epithelial injury, microbial translocation, and systemic immune activation. Insights from age-accelerated conditions such as HIV/SIV infection and inflammatory bowel disease are used to inform emerging models of T-cell-driven barrier decline in older adults.