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Peer-reviewedCC BYGeroScience

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

  • Christina M. Stevens1
  • Cecilia R. Schaaf2
  • Theodore M. DeConne3
  • Kylie Kavanagh4,2
4 affiliations
  1. 1Section on Comparative Medicine, Department of Pathology, Medical Center Blvd, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA. [email protected]
  2. 2Section on Comparative Medicine, Department of Pathology, Medical Center Blvd, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
  3. 3Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  4. 4College of Health and Medicine, University of Tasmania, Hobart, Australia
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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.

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Cite

BibTeXRIS
BibTeX
@article{stevens2026intestinal,
  title = {{Intestinal T cells in aging: implications for gut barrier integrity and inflammaging}},
  author = {Christina M. Stevens and Cecilia R. Schaaf and Theodore M. DeConne and Kylie Kavanagh},
  journal = {GeroScience},
  year = {2026},
  month = may,
  doi = {10.1007/s11357-026-02292-x},
  url = {https://doi.org/10.1007/s11357-026-02292-x},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Intestinal T cells in aging: implications for gut barrier integrity and inflammaging
AU  - Christina M. Stevens
AU  - Cecilia R. Schaaf
AU  - Theodore M. DeConne
AU  - Kylie Kavanagh
PY  - 2026
DA  - 2026/05/16
JO  - GeroScience
DO  - 10.1007/s11357-026-02292-x
UR  - https://doi.org/10.1007/s11357-026-02292-x
AB  - 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.
SN  - 2152-4041
SN  - 2331-3773
SN  - 2509-2715
SN  - 2509-2723
ER  -