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Microanatomical dissection of human intestinal T-cell immunity reveals site-specific changes in gut-associated lymphoid tissues over life
Open accessAbstract
Defining adaptive immunity with the complex structures of the human gastrointestinal (GI) tract over life is essential for understanding immune responses to ingested antigens, commensal and pathogenic microorganisms, and dysfunctions in disease. We present here an analysis of lymphocyte localization and T cell subset composition across the human GI tract including mucosal sites (jejunum, ileum, colon), gut-associated lymphoid tissues (isolated lymphoid follicles (ILFs), Peyer's patches (PPs), appendix), and mesenteric lymph nodes (MLNs) from a total of 68 donors spanning eight decades of life. In pediatric donors, ILFs and PP containing naïve T cells and regulatory T cells (Tregs) are prevalent in the jejunum and ileum, respectively; these decline in frequency with age, contrasting stable frequencies of ILFs and T cell subsets in the colon. In the mucosa, tissue resident memory T cells develop during childhood, and persist in high frequencies into advanced ages, while T cell composition changes with age in GALT and MLN. These spatial and temporal features of human intestinal T cell immunity define signatures that can be used to train predictive machine learning algorithms. Our findings demonstrate an anatomic basis for age-associated alterations in immune responses, and establish a quantitative baseline for intestinal immunity to define disease pathologies.
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“Tregs are present throughout the human body and their abundance in circulation and tissues is age dependent [264, 359].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [359]
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Metadata
- Authors
- Senda, T., Dogra, P., Granot, T., Furuhashi, K., Snyder, M. E., Carpenter, D. J., Szabo, P. A., Thapa, P., Miron, M., & Farber, D. L.
- Affiliations
- Columbia University Irving Medical Center (US)
- ORCID
- Venue
- Mucosal Immunology
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 12
- Issue
- 2
- Pages
- 378-389
- ISSN
- 1933-0219 (ISSN-L)
- PMC
- PMC6375790
- OpenAlex
- W2902016030
- Cited by
- 114
- References
- 50
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 12 · 2023: 12 · 2022: 11 · 2021: 26 · 2020: 16 · 2019: 11
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Mucosal Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (AI06697, AI100119)
- National Institute of Allergy and Infectious Diseases (U01AI100119, P01AI106697, R01AI100119, T32AI106711)
- National Center for Research Resources (S10RR027050)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- gut-associated lymphoid tissue, isolated lymphoid follicles, Peyer's patches, mesenteric lymph nodes, regulatory T cells, naive T cells, tissue-resident memory T cells, age-related immune changes, jejunum, ileum, colon, appendix, pediatric donors, machine learning training data
- MeSH terms
- Adult, Aging, Cells, Cultured, Child, Duodenum, Humans, Ileum, Immunity, Cellular, Intestinal Mucosa, Jejunum, Lymph Nodes, Organ Specificity, Peyer's Patches, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory
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